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  • 1.
    Agathangelidis, A.
    et al.
    Ist Sci San Raffaele, Div Expt Oncol, I-20132 Milan, Italy.;Ist Sci San Raffaele, Dept Oncohematol, I-20132 Milan, Italy.;Univ Vita Salute San Raffaele, Milan, Italy..
    Bystry, V.
    Masaryk Univ, Cent European Inst Technol, Brno, Czech Republic..
    Hadzidimitriou, A.
    CERTH, Inst Appl Biosci, Thessaloniki, Greece..
    Sutton, L. A.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Minga, E.
    CERTH, Inst Appl Biosci, Thessaloniki, Greece..
    Kienle, D.
    Univ Ulm, Dept Internal Med 3, D-89069 Ulm, Germany..
    Davis, Z.
    Royal Bournemouth Hosp, Dept Haematol, Bournemouth, Dorset, England..
    Yan, X. J.
    North Shore Long Isl Jewish Hlth Syst, Feinstein Inst Med Res, Manhasset, NY USA..
    Shanafelt, T.
    Mayo Clin, Dept Med, Dept Hematol, Rochester, MN USA..
    Boudjogra, M.
    Univ Paris 06, Hop Pitie Salpetriere, Dept Hematol, Paris, France.;Univ Paris 06, Hop Pitie Salpetriere, Paris, France..
    Plevova, K.
    Masaryk Univ, Cent European Inst Technol, Brno, Czech Republic.;Univ Hosp Brno, Brno, Czech Republic..
    Gounari, M.
    Ist Sci San Raffaele, Div Expt Oncol, I-20132 Milan, Italy.;Ist Sci San Raffaele, Dept Oncohematol, I-20132 Milan, Italy.;Univ Vita Salute San Raffaele, Milan, Italy..
    Xochelli, A.
    CERTH, Inst Appl Biosci, Thessaloniki, Greece..
    Navarro, A.
    Univ Barcelona, IDIBAPS, Unidad Hematopatol, Serv Anat Patol, Barcelona, Spain..
    Chatzouli, M.
    Nikea Gen Hosp, Dept Hematol, Piraeus, Greece..
    Pedersen, L. B.
    Rigshosp, Dept Hematol, DK-2100 Copenhagen, Denmark..
    Baliakas, Panagiotis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Scarfo, L.
    Ist Sci San Raffaele, Div Expt Oncol, I-20132 Milan, Italy.;Ist Sci San Raffaele, Dept Oncohematol, I-20132 Milan, Italy.;Univ Vita Salute San Raffaele, Milan, Italy..
    Rossi, D.
    Amedeo Avogadro Univ Eastern Piedmont, Dept Hematol, Novara, Italy..
    Veronese, S.
    Osped Niguarda Ca Granda, Niguarda Canc Ctr, Mol Pathol Unit, Milan, Italy.;Osped Niguarda Ca Granda, Niguarda Canc Ctr, Dept Hematol, Milan, Italy..
    Facco, M.
    Univ Padua, Sch Med, Hematol & Clin Immunol Branch, Dept Med, Padua, Italy..
    Bikos, V.
    Masaryk Univ, Cent European Inst Technol, Brno, Czech Republic..
    Karan-Djurasevic, T.
    Univ Belgrade, Inst Mol Genet & Genet Engn, Belgrade, Serbia..
    Pavlovic, S.
    Univ Kragujevac, Kragujevac, Serbia..
    Mansouri, Larry
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Poiron, C.
    Univ Montpellier, IMGT, LIGM, IGH, Montpellier, France..
    Chu, C. C.
    North Shore Long Isl Jewish Hlth Syst, Feinstein Inst Med Res, Manhasset, NY USA..
    Stalika, E.
    CERTH, Inst Appl Biosci, Thessaloniki, Greece..
    Giudicelli, V.
    Univ Montpellier, IMGT, LIGM, IGH, Montpellier, France..
    Panagiotidis, P.
    Univ Athens, Dept Propaedeut Med 1, Athens, Greece..
    Sudarikov, A.
    Natl Hematol Res Ctr, Dept Mol Hematol, Moscow, Russia..
    Anagnostopoulos, A.
    G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    Trentin, L.
    Univ Padua, Sch Med, Hematol & Clin Immunol Branch, Dept Med, Padua, Italy..
    Catherwood, M.
    Belfast City Hosp, Dept Hematooncol, Belfast BT9 7AD, Antrim, North Ireland..
    Montillo, M.
    Osped Niguarda Ca Granda, Niguarda Canc Ctr, Mol Pathol Unit, Milan, Italy.;Osped Niguarda Ca Granda, Niguarda Canc Ctr, Dept Hematol, Milan, Italy..
    Gaidano, G.
    Amedeo Avogadro Univ Eastern Piedmont, Dept Hematol, Novara, Italy..
    Campo, E.
    Univ Barcelona, IDIBAPS, Unidad Hematopatol, Serv Anat Patol, Barcelona, Spain..
    Geisler, C. H.
    Rigshosp, Dept Hematol, DK-2100 Copenhagen, Denmark..
    Langerak, A. W.
    Erasmus MC, Univ Med Ctr, Dept Immunol, Rotterdam, Netherlands..
    Pospisilova, S.
    Masaryk Univ, Cent European Inst Technol, Brno, Czech Republic.;Univ Hosp Brno, Brno, Czech Republic..
    Lefranc, M. P.
    Univ Montpellier, IMGT, LIGM, IGH, Montpellier, France..
    Chiorazzi, N.
    North Shore Long Isl Jewish Hlth Syst, Feinstein Inst Med Res, Manhasset, NY USA..
    Oscier, D.
    Royal Bournemouth Hosp, Dept Haematol, Bournemouth, Dorset, England..
    Jelinek, D. F.
    Mayo Clin, Dept Immunol, Rochester, MN USA..
    Stilgenbauer, S.
    Univ Ulm, Dept Internal Med 3, D-89069 Ulm, Germany..
    Belessi, C.
    Nikea Gen Hosp, Dept Hematol, Piraeus, Greece..
    Davi, F.
    Univ Paris 06, Hop Pitie Salpetriere, Dept Hematol, Paris, France.;Univ Paris 06, Hop Pitie Salpetriere, Paris, France..
    Rosenquist, Richard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Ghia, P.
    Ist Sci San Raffaele, Div Expt Oncol, I-20132 Milan, Italy.;Ist Sci San Raffaele, Dept Oncohematol, I-20132 Milan, Italy.;Univ Vita Salute San Raffaele, Milan, Italy..
    Darzentas, N.
    Masaryk Univ, Cent European Inst Technol, Brno, Czech Republic..
    Stamatopoulos, Kostas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. CERTH, Inst Appl Biosci, Thessaloniki, Greece.;G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    HIGHER-ORDER IMMUNOGLOBULIN SEQUENCE RELATIONS FOR MAJOR SUBSETS OF CHRONIC LYMPHOCYTIC LEUKEMIA: UNIQUENESS VERSUS EQUIVALENCE2015In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 100, p. 47-48Article in journal (Other academic)
  • 2. Agathangelidis, Andreas
    et al.
    Vardi, Anna
    Baliakas, Panagiotis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Hematology and Immunology.
    Stamatopoulos, Kostas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Stereotyped B-cell receptors in chronic lymphocytic leukemia2014In: Leukemia and Lymphoma, ISSN 1042-8194, E-ISSN 1029-2403, Vol. 55, no 10, p. 2252-2261Article, review/survey (Refereed)
    Abstract [en]

    Over the last decade, immunogenetic analysis of B-cell receptor immunoglobulins (BcR IGs) has proved to be a particularly fruitful field in chronic lymphocytic leukemia (CLL), not only for understanding disease pathogenesis but also for discriminating clinical subgroups with markedly distinct course and outcome. Of utmost importance was the identification of quasi-identical BcR IGs among unrelated patients with CLL, fittingly coined as "stereotypy," that set the wheels in motion for unraveling the role of antigen(s) in the selection and expansion of the leukemic clones. The categorization of CLL clones into "subsets" according to shared BcR IG structural characteristics provided a compartmentalized view of this otherwise heterogeneous disease, which eventually led to defining strikingly homogeneous groups of patients in terms of: (i) functional properties of the clonal BcR IGs, e. g. BcR reactivity and signaling; (ii) clonal genetic landscape, e. g. genomic aberrations, gene expression/methylation profiles, microRNA signatures; and (iii) clinical course and outcome. The remarkable restriction of the CLL IG gene repertoire, resulting to a great degree from the high impact of BcR IG stereotypy, may also prompt speculations regarding CLL ontogenesis. Overall, the BcR IG molecule justifiably lies at the heart of CLL clinical research, holding the promise of subset-tailored therapies.

  • 3.
    Baliakas, Panagiotis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Reappraising prognosis in chronic lymphocytic leukemia2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Chronic lymphocytic leukemia (CLL) exhibits remarkable clinical heterogeneity likely reflecting the underlying biological heterogeneity. The genetic landscape of CLL has been recently enriched with mutations within a number of genes proposed as novel prognostic markers. Mounting evidence also supports the pivotal role of the clonotypic B-cell receptor immunoglobulin (BcR IG) in the natural history of CLL. Interestingly, almost 30% of all CLL patients can be assigned to different patient subsets, each defined by expression of a distinct stereotyped BcR IG. Whether stereotyped subsets exhibit distinct clinical behavior is still an issue of debate. The aim of this thesis was to evaluate the prognostic relevance of recurrent gene mutations and to assess the clinicobiological associations and clinical impact of BcR IG stereotypy in CLL. In a cohort of 3490 patients, NOTCH1, SF3B1 and TP53 mutations were enriched within clinically aggressive cases carrying unmutated IGHV genes (U-CLL), frequently co-occurring with trisomy 12, del(11q) and del(17p), respectively. Of note, SF3B1 mutations increased in parallel with increasing timespan between diagnosis and mutational screening. NOTCH1 mutations, SF3B1 mutations and TP53 abnormalities (TP53abs, deletions and/or mutations) correlated with shorter time-to-first-treatment among early stage cases, while in multivariate analysis, only SF3B1 mutations and TP53abs retained independent significance. In a series of 8593 CLL patients, stereotyped subsets showed marked differences in demographics, clinical presentation, cytogenetic aberrations and gene mutational spectrum. Patients within a specific subset generally followed similar clinical courses, whereas patients in different stereotyped subsets—even when displaying similar IG somatic hypermutation status— experienced significantly different clinical outcome. In particular, subset #2 (IGHV3-21/IGLV3-21), the largest overall, was found to exhibit (i) a remarkably high incidence of SF3B1 mutations (44%), alluding to subset-biased acquisition of genomic aberrations, in the context of particular antigenic stimulation; and, (ii) a dismal clinical outcome, distinct from the remaining IGHV3-21 CLL. Our findings strongly support the adverse clinical impact of SF3B1 mutations in CLL in addition to TP53abs. BcR IG stereotypy also emerges as prognostically relevant, further highlighting that an immunogenetic sub-classification of CLL based on BcR IG configuration could refine patient risk stratification. 

  • 4.
    Baliakas, Panagiotis
    et al.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Agathangelidis, Andreas
    Hadzidimitriou, Anastasia
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Sutton, Lesley-Ann
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Minga, Eva
    Tsanousa, Athina
    Scarfo, Lydia
    Davis, Zadie
    Yan, Xiao-Jie
    Shanafelt, Tait
    Plevova, Karla
    Sandberg, Yorick
    Vojdeman, Fie Juhl
    Boudjogra, Myriam
    Tzenou, Tatiana
    Chatzouli, Maria
    Chu, Charles C.
    Veronese, Silvio
    Gardiner, Anne
    Mansouri, Larry
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Smedby, Karin E.
    Pedersen, Lone Bredo
    Moreno, Denis
    Van Lom, Kirsten
    Giudicelli, Veronique
    Francova, Hana Skuhrova
    Nguyen-Khac, Florence
    Panagiotidis, Panagiotis
    Juliusson, Gunnar
    Angelis, Lefteris
    Anagnostopoulos, Achilles
    Lefranc, Marie-Paule
    Facco, Monica
    Trentin, Livio
    Catherwood, Mark
    Montillo, Marco
    Geisler, Christian H.
    Langerak, Anton W.
    Pospisilova, Sarka
    Chiorazzi, Nicholas
    Oscier, David
    Jelinek, Diane F.
    Darzentas, Nikos
    Belessi, Chrysoula
    Davi, Frederic
    Ghia, Paolo
    Rosenquist, Richard Brandell
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Stamatopoulos, Kostas
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Not all IGHV3-21 chronic lymphocytic leukemias are equal: prognostic considerations2015In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 125, no 5, p. 856-859Article in journal (Refereed)
    Abstract [en]

    An unresolved issue in chronic lymphocytic leukemia (CLL) is whether IGHV3-21 gene usage, in general, or the expression of stereotyped B-cell receptor immunoglobulin defining subset # 2 (IGHV3-21/IGLV3-21), in particular, determines outcome for IGHV3-21-utilizing cases. We reappraised this issue in 8593 CLL patients of whom 437 (5%) used the IGHV3-21 gene with 254/437 (58%) classified as subset # 2. Within subset # 2, immunoglobulin heavy variable (IGHV)-mutated cases predominated, whereas non-subset # 2/IGHV3-21 was enriched for IGHV-unmutated cases (P =.002). Subset # 2 exhibited significantly shorter time-to-first-treatment (TTFT) compared with non-subset # 2/IGHV3-21 (22 vs 60 months, P =.001). No such difference was observed between non-subset # 2/IGHV3-21 vs the remaining CLL with similar IGHV mutational status. In conclusion, IGHV3-21 CLL should not be axiomatically considered a homogeneous entity with adverse prognosis, given that only subset # 2 emerges as uniformly aggressive, contrasting non-subset # 2/IGVH3-21 patients whose prognosis depends on IGHV mutational status as the remaining CLL.

  • 5.
    Baliakas, Panagiotis
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Hadzidimitriou, A.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Mattsson, Mattias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Xochelli, Aliki
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Sutton, L. A.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Minga, E.
    Ctr Res & Technol Hellas, Inst Appl Biosci, Thessaloniki, Greece..
    Scarfo, L.
    Ist Sci San Raffaele, Div Expt Oncol, I-20132 Milan, Italy.;Ist Sci San Raffaele, Dept Oncohematol, I-20132 Milan, Italy.;Fdn Ctr San Raffaele, Milan, Italy.;Univ Vita Salute San Raffaele, Milan, Italy..
    Rossi, D.
    Amedeo Avogadro Univ Eastern Piedmont, Dept Translat Med, Div Hematol, Novara, Italy..
    Davis, Z.
    Royal Bournemouth Hosp, Dept Haematol, Bournemouth, Dorset, England..
    Agathangelidis, A.
    Ist Sci San Raffaele, Div Expt Oncol, I-20132 Milan, Italy.;Ist Sci San Raffaele, Dept Oncohematol, I-20132 Milan, Italy.;Fdn Ctr San Raffaele, Milan, Italy.;Univ Vita Salute San Raffaele, Milan, Italy..
    Villamor, N.
    Hosp Clin Barcelona, Hemopathol Unit, Barcelona, Spain..
    Parker, H.
    Univ Southampton, Fac Med, Canc Sci, Southampton SO9 5NH, Hants, England..
    Kotaskova, J.
    Masaryk Univ, Cent European Inst Technol, Brno, Czech Republic.;Univ Hosp Brno, Brno, Czech Republic..
    Stalika, E.
    Ctr Res & Technol Hellas, Inst Appl Biosci, Thessaloniki, Greece.;G Papanicolaou Hosp, Hematol Dept, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    Plevova, K.
    Masaryk Univ, Cent European Inst Technol, Brno, Czech Republic.;Univ Hosp Brno, Brno, Czech Republic..
    Mansouri, Larry
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Cortese, Diego
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Navarro Lopez, A.
    Hosp Clin Barcelona, Hemopathol Unit, Barcelona, Spain..
    Delgado, J.
    Hosp Clin Barcelona, Dept Hematol, Barcelona, Spain..
    Larrayoz, M.
    Univ Southampton, Fac Med, Canc Sci, Southampton SO9 5NH, Hants, England..
    Anagnostopoulos, A.
    G Papanicolaou Hosp, Hematol Dept, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    Belessi, C.
    Nikea Gen Hosp, Dept Hematol, Piraeus, Greece..
    Smedby, K. E.
    Dept Med, Solna, Sweden.;Karolinska Inst, Clin Epidemiol Unit, Stockholm, Sweden..
    Juliusson, G.
    Lund Univ, Lund, Sweden.;Lund Stem Cell Ctr, Hosp Dept Hematol, Lund, Sweden..
    Strefford, J. C.
    Univ Southampton, Fac Med, Canc Sci, Southampton SO9 5NH, Hants, England..
    Pospisilova, S.
    Masaryk Univ, Cent European Inst Technol, Brno, Czech Republic.;Univ Hosp Brno, Brno, Czech Republic..
    Oscier, D.
    Royal Bournemouth Hosp, Dept Haematol, Bournemouth, Dorset, England..
    Gaidano, G.
    Amedeo Avogadro Univ Eastern Piedmont, Dept Translat Med, Div Hematol, Novara, Italy..
    Campo, E.
    Hosp Clin Barcelona, Hemopathol Unit, Barcelona, Spain.;Univ Barcelona, Dept Pathol, Barcelona, Spain..
    Ghia, P.
    Ist Sci San Raffaele, Div Expt Oncol, I-20132 Milan, Italy.;Ist Sci San Raffaele, Dept Oncohematol, I-20132 Milan, Italy.;Fdn Ctr San Raffaele, Milan, Italy.;Univ Vita Salute San Raffaele, Milan, Italy..
    Rosenquist, Richard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Stamatopoulos, Kostas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    REFINING PROGNOSIS OF CHRONIC LYMPHOCYTIC LEUKEMIA WITH SOMATICALLY HYPERMUTATED B-CELL RECEPTORS: A NOVEL PROGNOSTIC INDEX ON BEHALF OF THE EUROPEAN RESEARCH INITIATIVE ON CLL (ERIC)2015In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 100, p. 52-52Article in journal (Other academic)
  • 6.
    Baliakas, Panagiotis
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Hematology and Immunology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Hadzidimitriou, A.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Sutton, L. A.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Minga, E.
    Agathangelidis, A.
    Tsanousa, A.
    Scarfo, L.
    Davis, Z.
    Yan, X. J.
    Shanafelt, T.
    Plevova, K.
    Sandberg, Y.
    Vojdeman, F. J.
    Boudjogra, M.
    Tzenou, T.
    Chatzouli, M.
    Chu, C. C.
    Veronese, S.
    Gardiner, A.
    Mansouri, Larry
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Hematology and Immunology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Smedby, K. E.
    Pedersen, L. B.
    Moreno, D.
    Van Lom, K.
    Giudicelli, V.
    Francova, H. S.
    Nguyen-Khac, F.
    Panagiotidis, P.
    Juliusson, G.
    Angelis, L.
    Anagnostopoulos, A.
    Lefranc, M. P.
    Trentin, L.
    Catherwood, M.
    Montillo, M.
    Geisler, C.
    Langerak, A. W.
    Pospisilova, S.
    Chiorazzi, N.
    Oscier, D.
    Jelinek, D.
    Darzentas, N.
    Belessi, C.
    Davi, F.
    Ghia, P.
    Rosenquist, Richard Brandell
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Hematology and Immunology.
    Stamatopoulos, K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Not All IGHV3-21 CLL Are Equal: Subset #2 Displays a Distinctive Clinicobiological Profile with Remarkable Similarities to Subset #169, its Close Immunogenetic Relative2014In: Haematologica (online), ISSN 0390-6078, E-ISSN 1592-8721, Vol. 99, no S1, p. 48-49Article in journal (Other academic)
  • 7.
    Baliakas, Panagiotis
    et al.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Hadzidimitriou, A
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Sutton, Lesley Ann
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Rossi, D
    Minga, E
    Villamor, N
    Larrayoz, M
    Kminkova, J
    Agathangelidis, A
    Davis, Z
    Tausch, E
    Stalika, E
    Kantorova, B
    Mansouri, Larry
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Scarfò, L
    Cortese, Diego
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Navrkalova, V
    Rose-Zerilli, M J J
    Smedby, K E
    Juliusson, G
    Anagnostopoulos, A
    Makris, A M
    Navarro, A
    Delgado, J
    Oscier, D
    Belessi, C
    Stilgenbauer, S
    Ghia, P
    Pospisilova, S
    Gaidano, G
    Campo, E
    Strefford, J C
    Stamatopoulos, Kostas
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Rosenquist, Richard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Recurrent mutations refine prognosis in chronic lymphocytic leukemia2015In: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 29, p. 329-336Article in journal (Refereed)
    Abstract [en]

    Through the European Research Initiative on chronic lymphocytic leukemia (CLL) (ERIC), we screened 3490 patients with CLL for mutations within the NOTCH1 (n=3334), SF3B1 (n=2322), TP53 (n=2309), MYD88 (n=1080) and BIRC3 (n=919) genes, mainly at diagnosis (75%) and before treatment (>90%). BIRC3 mutations (2.5%) were associated with unmutated IGHV genes (U-CLL), del(11q) and trisomy 12, whereas MYD88 mutations (2.2%) were exclusively found among M-CLL. NOTCH1, SF3B1 and TP53 exhibited variable frequencies and were mostly enriched within clinically aggressive cases. Interestingly, as the timespan between diagnosis and mutational screening increased, so too did the incidence of SF3B1 mutations; no such increase was observed for NOTCH1 mutations. Regarding the clinical impact, NOTCH1 mutations, SF3B1 mutations and TP53 aberrations (deletion/mutation, TP53ab) correlated with shorter time-to-first-treatment (P<0.0001) in 889 treatment-naive Binet stage A cases. In multivariate analysis (n=774), SF3B1 mutations and TP53ab along with del(11q) and U-CLL, but not NOTCH1 mutations, retained independent significance. Importantly, TP53ab and SF3B1 mutations had an adverse impact even in U-CLL. In conclusion, we support the clinical relevance of novel recurrent mutations in CLL, highlighting the adverse impact of SF3B1 and TP53 mutations, even independent of IGHV mutational status, thus underscoring the need for urgent standardization/harmonization of the detection methods.

  • 8.
    Baliakas, Panagiotis
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Hadzidimitriou, Anastasia
    Ctr Res & Technol Hellas, Inst Appl Biosci, Thessaloniki, Greece..
    Agathangelidis, Andreas
    Univ Vita Salute San Raffaele, I-20132 Milan, Italy.;Ist Sci San Raffaele, Ist Ricovero & Cura Carattere Sci, Div Expt Oncol, Dept Oncohematol, I-20132 Milan, Italy..
    Rossi, Davide
    Amedeo Avogadro Univ Eastern Piedmont, Dept Translat Med, Div Haematol, Novara, Italy..
    Sutton, Lesley-Ann
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Kminkova, Jana
    Masaryk Univ, Cent European Inst Technol, Brno, Czech Republic.;Univ Hosp, Brno, Czech Republic..
    Scarfo, Lydia
    Univ Vita Salute San Raffaele, I-20132 Milan, Italy.;Ist Sci San Raffaele, Ist Ricovero & Cura Carattere Sci, Div Expt Oncol, Dept Oncohematol, I-20132 Milan, Italy..
    Pospisilova, Sarka
    Masaryk Univ, Cent European Inst Technol, Brno, Czech Republic.;Univ Hosp, Brno, Czech Republic..
    Gaidano, Gianluca
    Amedeo Avogadro Univ Eastern Piedmont, Dept Translat Med, Div Haematol, Novara, Italy..
    Stamatopoulos, Kostas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Ghia, Paolo
    Univ Vita Salute San Raffaele, I-20132 Milan, Italy.;Ist Sci San Raffaele, Ist Ricovero & Cura Carattere Sci, Div Expt Oncol, Dept Oncohematol, I-20132 Milan, Italy..
    Rosenquist, Richard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Prognostic relevance of MYD88 mutations in CLL: the jury is still out2015In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 126, no 8, p. 1043-1044Article in journal (Refereed)
  • 9.
    Baliakas, Panagiotis
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala Univ, Sci Life Lab, Dept Immunol Genet & Pathol, Uppsala, Sweden.;G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    Hadzidimitriou, Anastasia
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. CERTH, Inst Appl Biosci, Thessaloniki, Greece..
    Sutton, Lesley-Ann
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Minga, Eva
    CERTH, Inst Appl Biosci, Thessaloniki, Greece..
    Agathangelidis, Andreas
    Univ Vita Salute San Raffaele, I-20132 Milan, Italy.;Ist Sci San Raffaele, IRCCS, Div Mol Oncol, I-20132 Milan, Italy.;Ist Sci San Raffaele, IRCCS, Dept Oncohematol, I-20132 Milan, Italy..
    Nichelatti, Michele
    Osped Niguarda Ca Granda, Niguarda Canc Ctr, Mol Pathol Unit, Milan, Italy.;Osped Niguarda Ca Granda, Niguarda Canc Ctr, Dept Haematol, Milan, Italy..
    Tsanousa, Athina
    Aristotle Univ Thessaloniki, Dept Informat, GR-54006 Thessaloniki, Greece..
    Scarfo, Lydia
    Univ Vita Salute San Raffaele, I-20132 Milan, Italy.;Ist Sci San Raffaele, IRCCS, Div Mol Oncol, I-20132 Milan, Italy.;Ist Sci San Raffaele, IRCCS, Dept Oncohematol, I-20132 Milan, Italy..
    Davis, Zadie
    Royal Bournemouth Hosp, Dept Haematol, Bournemouth, Dorset, England..
    Yan, Xiao-Jie
    North Shore Long Isl Jewish Hlth Syst, Feinstein Inst Med Res, Manhasset, NY USA..
    Shanafelt, Tait
    Mayo Clin, Div Hematol, Dept Med, Rochester, MN USA..
    Plevova, Karla
    Masaryk Univ, Cent European Inst Technol, Brno, Czech Republic.;Univ Hosp Brno, Brno, Czech Republic..
    Sandberg, Yorick
    Erasmus MC, Univ Med Ctr, Dept Immunol, Rotterdam, Netherlands..
    Vojdeman, Fie Juhl
    Rigshosp, Dept Hematol, DK-2100 Copenhagen, Denmark..
    Boudjogra, Myriam
    Hop La Pitie Salpetriere, Serv Hematol Biol, Paris, France..
    Tzenou, Tatiana
    Univ Athens, Dept Propaedeut Med, Athens, Greece..
    Chatzouli, Maria
    Nikea Gen Hosp, Dept Hematol, Piraeus, Greece..
    Chu, Charles C.
    North Shore Long Isl Jewish Hlth Syst, Feinstein Inst Med Res, Manhasset, NY USA..
    Veronese, Silvio
    Osped Niguarda Ca Granda, Niguarda Canc Ctr, Mol Pathol Unit, Milan, Italy.;Osped Niguarda Ca Granda, Niguarda Canc Ctr, Dept Haematol, Milan, Italy..
    Gardiner, Anne
    Royal Bournemouth Hosp, Dept Haematol, Bournemouth, Dorset, England..
    Mansouri, Larry
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala Univ, Sci Life Lab, Dept Immunol Genet & Pathol, Uppsala, Sweden..
    Smedby, Karin E.
    Karolinska Inst, Dept Med, Clin Epidemiol Unit, Stockholm, Sweden..
    Pedersen, Lone Bredo
    Rigshosp, Dept Hematol, DK-2100 Copenhagen, Denmark..
    van Lom, Kirsten
    Erasmus MC, Univ Med Ctr, Dept Hematol, Rotterdam, Netherlands..
    Giudicelli, Veronique
    Univ Montpellier, IMGT Int ImMunoGeneT Informat Syst, LIGM, Inst Genet Humaine, F-34059 Montpellier, France..
    Francova, Hana Skuhrova
    Masaryk Univ, Cent European Inst Technol, Brno, Czech Republic.;Univ Hosp Brno, Brno, Czech Republic..
    Nguyen-Khac, Florence
    Hop La Pitie Salpetriere, Serv Hematol Biol, Paris, France..
    Panagiotidis, Panagiotis
    Univ Athens, Dept Propaedeut Med, Athens, Greece..
    Juliusson, Gunnar
    Lund Univ & Hosp, Dept Hematol, Lund Stem Cell Ctr, Lund, Sweden..
    Angelis, Lefteris
    Aristotle Univ Thessaloniki, Dept Informat, GR-54006 Thessaloniki, Greece..
    Anagnostopoulos, Achilles
    G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    Lefranc, Marie-Paule
    Univ Montpellier, IMGT Int ImMunoGeneT Informat Syst, LIGM, Inst Genet Humaine, F-34059 Montpellier, France..
    Facco, Monica
    Univ Padua, Sch Med, Dept Med, Hematol & Clin Immunol Branch, I-35100 Padua, Italy.;Venetian Inst Mol Med, Padua, Italy..
    Trentin, Livio
    Univ Padua, Sch Med, Dept Med, Hematol & Clin Immunol Branch, I-35100 Padua, Italy.;Venetian Inst Mol Med, Padua, Italy..
    Catherwood, Mark
    Belfast City Hosp, Dept Haematooncol, Belfast BT9 7AD, Antrim, North Ireland..
    Montillo, Marco
    Osped Niguarda Ca Granda, Niguarda Canc Ctr, Mol Pathol Unit, Milan, Italy.;Osped Niguarda Ca Granda, Niguarda Canc Ctr, Dept Haematol, Milan, Italy..
    Geisler, Christian H.
    Rigshosp, Dept Hematol, DK-2100 Copenhagen, Denmark..
    Langerak, Anton W.
    Erasmus MC, Univ Med Ctr, Dept Immunol, Rotterdam, Netherlands..
    Pospisilova, Sarka
    Masaryk Univ, Cent European Inst Technol, Brno, Czech Republic.;Univ Hosp Brno, Brno, Czech Republic..
    Chiorazzi, Nicholas
    North Shore Long Isl Jewish Hlth Syst, Feinstein Inst Med Res, Manhasset, NY USA..
    Oscier, David
    Royal Bournemouth Hosp, Dept Haematol, Bournemouth, Dorset, England..
    Jelinek, Diane F.
    Mayo Clin, Dept Immunol, Dept Med, Rochester, MN USA..
    Darzentas, Nikos
    Masaryk Univ, Cent European Inst Technol, Brno, Czech Republic..
    Belessi, Chrysoula
    Nikea Gen Hosp, Dept Hematol, Piraeus, Greece..
    Davi, Frederic
    Hop La Pitie Salpetriere, Serv Hematol Biol, Paris, France..
    Rosenquist Barndell, Richard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Ghia, Paolo
    Univ Vita Salute San Raffaele, I-20132 Milan, Italy.;Ist Sci San Raffaele, IRCCS, Div Mol Oncol, I-20132 Milan, Italy.;Ist Sci San Raffaele, IRCCS, Dept Oncohematol, I-20132 Milan, Italy..
    Stamatopoulos, Kostas
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece.;CERTH, Inst Appl Biosci, Thessaloniki, Greece..
    Clinical effect of stereotyped B-cell receptor immunoglobulins in chronic lymphocytic leukaemia: a retrospective multicentre study2014In: LANCET HAEMATOLOGY, ISSN 2352-3026, Vol. 1, no 2, p. E74-E84Article in journal (Refereed)
    Abstract [en]

    Background About 30% of cases of chronic lymphocytic leukaemia (CLL) carry quasi-identical B-cell receptor immunoglobulins and can be assigned to distinct stereotyped subsets. Although preliminary evidence suggests that B-cell receptor immunoglobulin stereotypy is relevant from a clinical viewpoint, this aspect has never been explored in a systematic manner or in a cohort of adequate size that would enable clinical conclusions to be drawn. Methods For this retrospective, multicentre study, we analysed 8593 patients with CLL for whom immunogenetic data were available. These patients were followed up in 15 academic institutions throughout Europe (in Czech Republic, Denmark, France, Greece, Italy, Netherlands, Sweden, and the UK) and the USA, and data were collected between June 1, 2012, and June 7, 2013. We retrospectively assessed the clinical implications of CLL B-cell receptor immunoglobulin stereotypy, with a particular focus on 14 major stereotyped subsets comprising cases expressing unmutated (U-CLL) or mutated (M-CLL) immunoglobulin heavy chain variable genes. The primary outcome of our analysis was time to first treatment, defined as the time between diagnosis and date of first treatment. Findings 2878 patients were assigned to a stereotyped subset, of which 1122 patients belonged to one of 14 major subsets. Stereotyped subsets showed significant differences in terms of age, sex, disease burden at diagnosis, CD38 expression, and cytogenetic aberrations of prognostic significance. Patients within a specific subset generally followed the same clinical course, whereas patients in different stereotyped subsets-despite having the same immunoglobulin heavy variable gene and displaying similar immunoglobulin mutational status-showed substantially different times to first treatment. By integrating B-cell receptor immunoglobulin stereotypy (for subsets 1, 2, and 4) into the well established Dohner cytogenetic prognostic model, we showed these, which collectively account for around 7% of all cases of CLL and represent both U-CLL and M-CLL, constituted separate clinical entities, ranging from very indolent (subset 4) to aggressive disease (subsets 1 and 2). Interpretation The molecular classification of chronic lymphocytic leukaemia based on B-cell receptor immunoglobulin stereotypy improves the Dohner hierarchical model and refines prognostication beyond immunoglobulin mutational status, with potential implications for clinical decision making, especially within prospective clinical trials.

  • 10.
    Baliakas, Panagiotis
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Hematology and Immunology.
    Iskas, Michalis
    Gardiner, Anne
    Davis, Zadie
    Plevova, Karla
    Nguyen-Khac, Florence
    Malcikova, Jitka
    Anagnostopoulos, Achilles
    Glide, Sharron
    Mould, Sarah
    Stepanovska, Kristina
    Brejcha, Martin
    Belessi, Chrysoula
    Davi, Frederic
    Pospisilova, Sarka
    Athanasiadou, Anastasia
    Stamatopoulos, Kostas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Oscier, David
    Chromosomal translocations and karyotype complexity in chronic lymphocytic leukemia: A systematic reappraisal of classic cytogenetic data2014In: American Journal of Hematology, ISSN 0361-8609, E-ISSN 1096-8652, Vol. 89, no 3, p. 249-255Article in journal (Refereed)
    Abstract [en]

    The significance of chromosomal translocations (CTRAs) and karyotype complexity (KC) in chronic lymphocytic leukemia (CLL) remains uncertain. To gain insight into these issues, we evaluated a series of 1001 CLL cases with reliable classic cytogenetic data obtained within 6 months from diagnosis before any treatment. Overall, 320 cases were found to carry 1 CTRAs. The most frequent chromosome breakpoints were 13q, followed by 14q, 18q, 17q, and 17p; notably, CTRAs involving chromosome 13q showed a wide spectrum of translocation partners. KC (3 aberrations) was detected in 157 cases and significantly (P<0.005) associated with unmutated IGHV genes and aberrations of chromosome 17p. Furthermore, it was identified as an independent prognostic factor for shorter time-to-first-treatment. CTRAs were assigned to two categories (i) CTRAs present in the context of KC, often with involvement of chromosome 17p aberrations, occurring mostly in CLL with unmutated IGHV genes; in such cases, we found that KC rather than the presence of CTRAs per se negatively impacts on survival; (ii) CTRAs in cases without KC, having limited if any impact on survival. On this evidence, we propose that all CTRAs in CLL are not equivalent but rather develop by different processes and are associated with distinct clonal behavior. Am. J. Hematol. 89:249-255, 2014. (c) 2013 Wiley Periodicals, Inc.

  • 11.
    Baliakas, Panagiotis
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Jeronim, Sabine
    MLL Munich Leukemia Lab, Munich, Germany.
    Iskas, Michalis
    G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece; G Papanicolaou Hosp, HCT Unit, Exochi, Greece.
    Puiggros, Anna
    Fdn IMIM Hosp del Mar, Barcelona, Spain.
    Plevova, Karla
    Masaryk Univ, Cent European Inst Technol CEITEC, Brno, Czech Republic.
    Xochelli, Aliki
    Ctr Res & Technol Hellas, Inst Appl Biosci, Thessaloniki, Greece.
    Delgado, Julio
    Univ Barcelona, Seccio Hematopatol, Hosp Clin, Inst Invest Biomed Augusti Pi & Sunyer IDIBAPS, Barcelona, Spain.
    Kotaskova, Jana
    Masaryk Univ, CEITEC, Brno, Czech Republic; Univ Hosp Brno, Dept Internal Med Hematol & Oncol, Brno, Czech Republic; Med Fac MU, Brno, Czech Republic.
    Stalika, Evangelia
    CERTH, Thermi, Greece.
    Costa, Pablo Abrisqueta
    Vall dHebron Inst Oncol, Barcelona, Spain.
    Durechova, Kristina
    Masaryk Univ, Cent European Inst Technol CEITEC, Brno, Czech Republic.
    Papaioannou, Giorgos
    G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece; G Papanicolaou Hosp, HCT Unit, Exochi, Greece.
    Collado, Rosa
    Consorcio Hosp Gen Univ, Serv Hematol, Valencia, Spain.
    Doubek, Michael
    Univ Hosp Brno, Brno, Czech Republic.
    Jose Calasanz, M.
    Univ Navarra, Dept Genet, Serv Citogenet, Pamplona, Spain.
    Ruiz-Xiville, Neus
    Univ Autonoma Barcelona, Inst Recerca Leucemia Josep Carreras IJC, Hosp Germans Trias & Pujol, Serv Lab Hematol,ICO, Badalona, Spain.
    Moreno, Carol
    Hosp Santa Creu & Sant Pau, Barcelona, Spain.
    Anagnostopoulos, Achilles
    George Papanicolaou Hosp, Haematol Dept, BMT Unit, Gene & Cell Therapy Ctr, Exochi, Greece.
    Stavroyianni, Niki
    G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece; G Papanicolaou Hosp, HCT Unit, Exochi, Greece.
    Kater, Arnon
    Univ Amsterdam, Amsterdam, Netherlands.
    Espinet, Blanca
    Fdn IMIM Hosp del Mar, Barcelona, Spain.
    Pospisilova, Sarka
    Masaryk Univ, CEITEC, Brno, Czech Republic; Univ Hosp Brno, Dept Internal Med Hematol & Oncol, Brno, Czech Republic; Med Fac MU, Brno, Czech Republic.
    Athanasiadou, Anastasia
    G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece; G Papanicolaou Hosp, HCT Unit, Exochi, Greece.
    Stamatopoulos, Kostas
    Ctr Res & Technol Hellas, Thermi, Greece.
    Haferlach, Claudia
    MLL Munich Leukemia Lab, Munich, Germany.
    Cytogenetic complexity in chronic lymphocytic leukemia: definitions, associations with other bio-markers and clinical impact2017In: Leukemia and Lymphoma, ISSN 1042-8194, E-ISSN 1029-2403, Vol. 58, no Supplement: 1, p. 65-66Article in journal (Other academic)
  • 12.
    Baliakas, Panagiotis
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Mattsson, Mattias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Hadzidimitriou, A.
    Inst Appl Biosci, Thessaloniki, Greece..
    Minga, E.
    Inst Appl Biosci, Thessaloniki, Greece..
    Agathangelidis, A.
    Univ Vita Salute San Raffaele, Milan, Italy.;Ist Sci San Raffaele, Div Expt Oncol, Milan, Italy.;Ist Sci San Raffaele, Dept Oncohematol, Milan, Italy..
    Sutton, L. A.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Scarfo, L.
    Univ Vita Salute San Raffaele, Milan, Italy.;Ist Sci San Raffaele, Div Expt Oncol, Milan, Italy.;Ist Sci San Raffaele, Dept Oncohematol, Milan, Italy..
    Davis, Z.
    Royal Bournemouth Hosp, Dept Haematol, Bournemouth, Dorset, England..
    Yan, X. J.
    Northwell Hlth, Feinstein Inst Med Res, New York, NY USA..
    Plevova, K.
    Masaryk Univ, Cent European Inst Technol, Brno, Czech Republic.;Univ Hosp Brno, Brno, Czech Republic..
    Sandberg, Y.
    Univ Med Ctr Rotterdam, Erasmus MC, Dept Immunol, Rotterdam, Netherlands..
    Vojdeman, F. Juhl
    Rigshosp, Dept Hematol, Copenhagen, Denmark..
    Tzenou, T.
    Univ Athens, Dept Propaedeut Med 1, Athens, Greece..
    Chu, C. C.
    Northwell Hlth, Feinstein Inst Med Res, New York, NY USA..
    Veroneze, S.
    Osped Niguarda Ca Granda, Niguarda Canc Ctr, Mol Pathol Unit, Milan, Italy.;Osped Niguarda Ca Granda, Niguarda Canc Ctr, Dept Haematol, Milan, Italy..
    Mansouri, Larry
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Smedby, K. E.
    Dept Med, Solna, Sweden.;Karolinska Inst, Clin Epidemiol Unit, Stockholm, Sweden..
    Giudicelli, V.
    Univ Montpellier, IMGT, LIGM, IGH, Montpellier, France..
    Nguyen-Khac, F.
    Dept Hematol, Paris, France.;Univ Paris 06, Hop Pitie Salpetriere, Paris, France..
    Panagiotidis, P.
    Univ Athens, Dept Propaedeut Med 1, Athens, Greece..
    Juliusson, G.
    Lund Univ, Lund, Sweden.;Lund Stem Cell Ctr, Hosp Dept Hematol, Lund, Sweden..
    Anagnostopoulos, A.
    G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    Lefranc, M. P.
    Univ Montpellier, IMGT, LIGM, IGH, Montpellier, France..
    Trentin, L.
    Univ Padua, Dept Med, Hematol & Clin Immunol Branch, Sch Med, Padua, Italy.;Venetian Inst Mol Med, Padua, Italy..
    Catherwood, M.
    Belfast City Hosp, Dept Hematooncol, Belfast, Antrim, North Ireland..
    Montillo, M.
    Osped Niguarda Ca Granda, Niguarda Canc Ctr, Mol Pathol Unit, Milan, Italy.;Osped Niguarda Ca Granda, Niguarda Canc Ctr, Dept Haematol, Milan, Italy..
    Niemann, C. U.
    Rigshosp, Dept Hematol, Copenhagen, Denmark..
    Langerak, A. W.
    Univ Med Ctr Rotterdam, Erasmus MC, Dept Immunol, Rotterdam, Netherlands..
    Pospisilova, S.
    Masaryk Univ, Cent European Inst Technol, Brno, Czech Republic.;Univ Hosp Brno, Brno, Czech Republic..
    Stavroyianni, N.
    G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    Chiorazzi, N.
    Northwell Hlth, Feinstein Inst Med Res, New York, NY USA..
    Oscier, D.
    Royal Bournemouth Hosp, Dept Haematol, Bournemouth, Dorset, England..
    Jelinek, D. F.
    Mayo Clin, Dept Immunol, Rochester, MN USA..
    Shanafelt, T.
    Mayo Clin, Dept Med, Div Hematol, Rochester, MN USA..
    Darzentas, N.
    Masaryk Univ, Cent European Inst Technol, Brno, Czech Republic..
    Belessi, C.
    Nikea Gen Hosp, Dept Hematol, Piraeus, Greece..
    Davi, F.
    Dept Hematol, Paris, France.;Univ Paris 06, Hop Pitie Salpetriere, Paris, France..
    Ghia, P.
    Univ Vita Salute San Raffaele, Milan, Italy.;Ist Sci San Raffaele, Div Expt Oncol, Milan, Italy.;Ist Sci San Raffaele, Dept Oncohematol, Milan, Italy..
    Rosenquist, Richard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Stamatopoulos, Kostas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Inst Appl Biosci, Thessaloniki, Greece.;G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    No Improvement In Long-Term Overall Survival After The Introduction Of Chemo(Immuno)Therapy For Chronic Lymphocytic Leukemia Patients Belonging To Stereotyped Subset #22016In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 101, p. 231-231Article in journal (Other academic)
  • 13.
    Baliakas, Panagiotis
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Mattsson, Mattias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Stamatopoulos, Kostas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Rosenquist Brandell, Richard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Prognostic indices in chronic lymphocytic leukaemia: where do we stand how do we proceed?2016In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 279, no 4, p. 347-357Article, review/survey (Refereed)
    Abstract [en]

    The remarkable clinical heterogeneity in chronic lymphocytic leukaemia (CLL) has highlighted the need for prognostic and predictive algorithms that can be employed in clinical practice to assist patient management and therapy decisions. Over the last 20 years, this research field has been rewarding and many novel prognostic factors have been identified, especially at the molecular genetic level. Whilst detection of recurrent cytogenetic aberrations and determination of the immunoglobulin heavy variable gene somatic hypermutation status have an established role in outcome prediction, next-generation sequencing has recently revealed novel mutated genes with clinical relevance (e.g. NOTCH1, SF3B1 and BIRC3). Efforts have been made to combine variables into prognostic indices; however, none has been universally adopted. Although a unifying model for all groups of patients and in all situations is appealing, this may prove difficult to attain. Alternatively, focused efforts on patient subgroups in the same clinical context and at certain clinically relevant 'decision points', that is at diagnosis and at initiation of first-line or subsequent treatments, may provide a more accurate approach. In this review, we discuss the advantages and disadvantages as well as the clinical applicability of three recently proposed prognostic models, the MD Anderson nomogram, the integrated cytogenetic and mutational model and the CLL-international prognostic index. We also consider future directions taking into account novel aspects of the disease, such as the tumour microenvironment and the dynamics of (sub)clonal evolution. These aspects are particularly relevant in view of the increasing number of new targeted therapies that have recently emerged.

  • 14.
    Baliakas, Panagiotis
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Moreno, Carol
    Hosp Santa Creu & Sant Pau, Barcelona, Spain.
    Cuellar, Carolina
    St Pau Hosp, Barcelona, Spain.
    Scarfo, Lydia
    Osped San Raffaele, Segrate, Italy.
    Ghia, Paolo
    Univ Vita Salute San Raffaele, Milan, Italy; IRCCS Ist Sci San Raffaele, Milan, Italy.
    Brandell, Richard Rosenquist
    Karolinska Inst, Stockholm, Sweden.
    Mattsson, Mattias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Vicente, Eva Puy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Is FCR the treatment of choice for IGHV mutated CLL without poor FISH cytogenetics?2017In: Leukemia and Lymphoma, ISSN 1042-8194, E-ISSN 1029-2403, Vol. 58, no Supplement: 1, p. 170-171Article in journal (Other academic)
  • 15.
    Baliakas, Panagiotis
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Puiggros, A.
    Hosp del Mar, Lab Citogenet Mol, Serv Patol, Barcelona, Spain.;Spanish Cooperat Grp Hematol Cytogenet, Barcelona, Spain..
    Xochelli, Aliki
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Sutton, L. -A
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Nguyen-Khac, F.
    Univ Paris 06, Hop Pitie Salpetriere, Hematol Dept, Paris, France.;Univ Paris 06, Hop Pitie Salpetriere, Paris, France..
    Gardiner, A.
    Royal Bournemouth Hosp, Dept Haematol, Bournemouth, Dorset, England..
    Plevova, K.
    Masaryk Univ, Cent European Inst Technol, Brno, Czech Republic.;Univ Hosp Brno, Brno, Czech Republic..
    Ortega, M.
    Spanish Cooperat Grp Hematol Cytogenet, Barcelona, Spain.;Hosp Univ Vall dHebron, Barcelona, Spain..
    Collado, R.
    Spanish Cooperat Grp Hematol Cytogenet, Barcelona, Spain.;Consorcio Hosp Gen Univ Valencia, Valencia, Spain..
    Gonzalez, T.
    Spanish Cooperat Grp Hematol Cytogenet, Barcelona, Spain.;Fdn Publ Galega Med Xen, Santiago De Compostela, Spain..
    Granada, I.
    Spanish Cooperat Grp Hematol Cytogenet, Barcelona, Spain.;Hosp Badalona Germans Trias & Pujol, Badalona, Spain..
    Luno, E.
    Spanish Cooperat Grp Hematol Cytogenet, Barcelona, Spain.;Hosp Univ Cent Asturias, Oviedo, Spain..
    Kotaskova, J.
    Masaryk Univ, Cent European Inst Technol, Brno, Czech Republic.;Univ Hosp Brno, Brno, Czech Republic..
    Davis, Z.
    Royal Bournemouth Hosp, Dept Haematol, Bournemouth, Dorset, England..
    Anagnostopoulos, A.
    G Papanicolaou Hosp, Hematol Dept, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    Strefford, J.
    Univ Southampton, Fac Med, Canc Sci, Southampton SO9 5NH, Hants, England..
    Pospisilova, S.
    Masaryk Univ, Cent European Inst Technol, Brno, Czech Republic.;Univ Hosp Brno, Brno, Czech Republic..
    Davi, F.
    Univ Paris 06, Hop Pitie Salpetriere, Hematol Dept, Paris, France.;Univ Paris 06, Hop Pitie Salpetriere, Paris, France..
    Athanasiadou, A.
    G Papanicolaou Hosp, Hematol Dept, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    Rosenquist, Richard Brandell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Oscier, D.
    Royal Bournemouth Hosp, Dept Haematol, Bournemouth, Dorset, England..
    Sola, B. Espinet
    Hosp del Mar, Lab Citogenet Mol, Serv Patol, Barcelona, Spain.;Spanish Cooperat Grp Hematol Cytogenet, Barcelona, Spain..
    Stamatopoulos, Kostas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    ADDITIONAL TRISOMIES AMONGST PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA CARRYING TRISOMY 12: THE PARTNER CHROMOSOME MAKES A DIFFERENCE2015In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 100, p. 224-224Article in journal (Other academic)
  • 16.
    Baliakas, Panagiotis
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Puiggros, Anna
    Hosp Mar, Lab Citogenet Mol Servei Patol, Barcelona, Spain.;IMIM Hosp Mar, Canc Res Program, Grp Recerca Translac Neoplasies Hematol, Barcelona, Spain..
    Xochelli, Aliki
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. CERTH, Inst Appl Biosci, Thessaloniki, Greece..
    Sutton, Lesley-Ann
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Nguyen-Khac, Florence
    Hop La Pitie Salpetriere, AP HP, Dept Hematol, Paris, France.;Univ Paris 06, UMRS 1138, Paris, France..
    Gardiner, Anne
    Royal Bournemouth Hosp, Dept Haematol, Bournemouth, Dorset, England..
    Plevova, Karla
    Univ Hosp Brno, Brno, Czech Republic..
    Minga, Eva
    CERTH, Inst Appl Biosci, Thessaloniki, Greece..
    Hadzidimitriou, Anastasia
    CERTH, Inst Appl Biosci, Thessaloniki, Greece..
    Walewska, Renata
    Royal Bournemouth Hosp, Dept Haematol, Bournemouth, Dorset, England..
    McCarthy, Helen
    Royal Bournemouth Hosp, Dept Haematol, Bournemouth, Dorset, England..
    Ortega, Margarita
    Hosp Univ Vall Hebron, Barcelona, Spain..
    Collado, Rosa
    Consorcio Hosp Gen Univ Valencia, Valencia, Spain..
    Gonzalez, Teresa
    Fdn Publ Galega Med Xenom, Santiago De Compostela, Spain..
    Granada, Isabel
    Univ Autonoma Barcelona, ICO Hosp Gerans Trias & Pujol, Inst Recerca Leucemia Josep Carreras IJC, Badalona, Spain..
    Luno, Elisa
    Hosp Univ Cent Asturias, Oviedo, Spain..
    Kotaskova, Jana
    Masaryk Univ, Cent European Inst Technol, CS-60177 Brno, Czech Republic.;Univ Hosp Brno, Brno, Czech Republic..
    Moysiadis, Theodoros
    CERTH, Inst Appl Biosci, Thessaloniki, Greece..
    Davis, Zadie
    Stavroyianni, Niki
    G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    Anagnostopoulos, Achilles
    G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    Strefford, Jonathan C.
    Univ Southampton, Fac Med, Canc Sci, Southampton SO9 5NH, Hants, England..
    Pospisilova, Sarka
    Masaryk Univ, Cent European Inst Technol, CS-60177 Brno, Czech Republic..
    Davi, Frederic
    Athanasiadou, Anastasia
    G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    Rosenquist, Richard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Oscier, David
    Royal Bournemouth Hosp, Dept Haematol, Bournemouth, Dorset, England..
    Espinet, Blanca
    Hosp Mar, Lab Citogenet Mol Servei Patol, Barcelona, Spain.;IMIM Hosp Mar, Canc Res Program, Grp Recerca Translac Neoplasies Hematol, Barcelona, Spain..
    Stamatopoulos, Kostas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. CERTH, Inst Appl Biosci, Thessaloniki, Greece..
    Additional trisomies amongst patients with chronic lymphocytic leukemia carrying trisomy 12: the accompanying chromosome makes a difference2016In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 101, no 7, p. 299-302Article in journal (Refereed)
  • 17.
    Baliakas, Panagiotis
    et al.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Strefford, Jonathan C.
    Bikos, Vasilis
    Parry, Marina
    Stamatopoulos, Kostas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Oscier, David
    Splenic marginal-zone lymphoma: ontogeny and genetics2015In: Leukemia and Lymphoma, ISSN 1042-8194, E-ISSN 1029-2403, Vol. 56, no 2, p. 301-310Article, review/survey (Refereed)
    Abstract [en]

    Splenic marginal-zone lymphoma (SMZL) is a rare tumor that has recently emerged as a prototype for how the interplay between genetics and environment shapes the natural history of lymphomas. Indeed, the recent identification of molecular immunogenetic subgroups within SMZL may prove to be relevant not only for the sub-classification of the disease but also for improved understanding of the underlying biology. In contrast to other B-cell lymphomas, SMZL lacks a characteristic genetic lesion, although the majority of cases harbor genomic aberrations, as recently revealed by high-throughput studies that identified recurrent genetic aberrations, several in pathways related to marginal-zone differentiation and B-cell signaling. Here we provide an overview of recent research into the molecular and cellular biology of SMZL and related disorders, with special emphasis on immunogenetics and genomic aberrations, and discuss the value of molecular and cellular markers for the diagnosis and differential diagnosis of these entities.

  • 18.
    Baliakas, Panagiotis
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Xochelli, Aliki
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. ;G Papanicolaou Hosp, Hematol Dept, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece.;CERTH, Inst Appl Biosci, Thessaloniki, Greece..
    Minga, E.
    CERTH, Inst Appl Biosci, Thessaloniki, Greece..
    Karavalakis, G.
    G Papanicolaou Hosp, Hematol Dept, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    Athanasiadou, A.
    G Papanicolaou Hosp, Hematol Dept, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    Stalika, E.
    CERTH, Inst Appl Biosci, Thessaloniki, Greece..
    Douka, V.
    G Papanicolaou Hosp, Hematol Dept, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    Protopappa, M.
    Gen Hosp Serres, Hematol Dept, Serres, Greece..
    Mpanti, A.
    Papageorgiou Hosp, Dept Hematol, Thessaloniki, Greece..
    Kotsianidis, I.
    Democritus Univ Thrace, Dept Hematol, Alexandroupolis, Greece..
    Papaioannou, M.
    Aristotle Univ Thessaloniki, AHEPA Hosp, Dept Hematol, Thessaloniki, Greece..
    Stavroyianni, N.
    G Papanicolaou Hosp, Hematol Dept, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    Anagnostopoulos, A.
    G Papanicolaou Hosp, Hematol Dept, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    Belessi, C.
    Nikea Gen Hosp, Dept Hematol, Piraeus, Greece..
    Hadzidimitriou, A.
    CERTH, Inst Appl Biosci, Thessaloniki, Greece..
    Stamatopoulos, Kostas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. G Papanicolaou Hosp, Hematol Dept, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece.;CERTH, Inst Appl Biosci, Thessaloniki, Greece..
    Hypogammaglobulinemia In Chronic Lymphocytic Leukemia: Clinicobiological Associations2016In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 101, p. 438-438Article in journal (Other academic)
  • 19.
    Bhoi, Sujata
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Baliakas, Panagiotis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Cortese, Diego
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Mattsson, Mattias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Engvall, Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Smedby, Karin E.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Juliusson, Gunnar
    Sutton, Lesley-Ann
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Mansouri, Larry
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    UGT2B17 expression: a novel prognostic marker within IGHV-mutated chronic lymphocytic leukemia?2016In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 101, no 2, p. E63-E65Article in journal (Refereed)
    Abstract
  • 20.
    Bikos, Vasilis
    et al.
    G Papanicolaou Hosp, Hematol Dept, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece.;Masaryk Univ, Cent European Inst Technol, Brno, Czech Republic..
    Karypidou, Maria
    G Papanicolaou Hosp, Hematol Dept, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece.;CERTH, Inst Appl Biosci, Thessaloniki, Greece..
    Stalika, Evangelia
    CERTH, Inst Appl Biosci, Thessaloniki, Greece..
    Baliakas, Panagiotis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. G Papanicolaou Hosp, Hematol Dept, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    Xochelli, Aliki
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. CERTH, Inst Appl Biosci, Thessaloniki, Greece..
    Sutton, Lesley-Ann
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Papadopoulos, George
    CERTH, Informat Technol Inst, Thessaloniki, Greece..
    Agathangelidis, Andreas
    Univ Vita Salute San Raffaele, Div Expt Oncol, Milan, Italy.;Univ Vita Salute San Raffaele, Dept Oncohematol, Milan, Italy.;Ist Sci San Raffaele, Milan, Italy..
    Papadopoulou, Evdoxia
    CERTH, Informat Technol Inst, Thessaloniki, Greece..
    Davis, Zadie
    Royal Bournemouth Hosp, Dept Haematol, Bournemouth, Dorset, England..
    Algara, Patricia
    Hosp Virgen Salud, Dept Pathol, Toledo, OH, Spain..
    Kanellis, George
    Evangelismos Med Ctr, Hematopathol Dept, Athens, Greece..
    Traverse-Glehen, Alexandra
    Univ Lyon, Hosp Civils Lyon, Dept Pathol & Hematol, Lyon, France..
    Mollejo, Manuela
    Hosp Virgen Salud, Dept Pathol, Toledo, OH, Spain..
    Anagnostopoulos, Achilles
    G Papanicolaou Hosp, Hematol Dept, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    Ponzoni, Maurilio
    Ist Sci San Raffaele, Pathol Unit, I-20132 Milan, Italy..
    Gonzalez, David
    Inst Canc Res, Sect Haematooncol, London SW3 6JB, England..
    Pospisilova, Sarka
    Masaryk Univ, Cent European Inst Technol, Brno, Czech Republic..
    Matutes, Estella
    Inst Canc Res, Sect Haematooncol, London SW3 6JB, England..
    Angel Piris, Miguel
    Hosp Univ Marques de Valdecilla, Santander, Spain..
    Papadaki, Theodora
    Evangelismos Med Ctr, Hematopathol Dept, Athens, Greece..
    Ghia, Paolo
    Univ Vita Salute San Raffaele, Div Expt Oncol, Milan, Italy.;Univ Vita Salute San Raffaele, Dept Oncohematol, Milan, Italy.;Ist Sci San Raffaele, Milan, Italy..
    Rosenquist, Richard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Oscier, David
    Royal Bournemouth Hosp, Dept Haematol, Bournemouth, Dorset, England..
    Darzentas, Nikos
    Masaryk Univ, Cent European Inst Technol, Brno, Czech Republic..
    Tzovaras, Dimitrios
    CERTH, Informat Technol Inst, Thessaloniki, Greece..
    Belessi, Chrysoula
    Nikea Gen Hosp, Hematol Dept, Piraeus, Greece..
    Hadzidimitriou, Anastasia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. CERTH, Inst Appl Biosci, Thessaloniki, Greece..
    Stamatopoulos, Kostas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. G Papanicolaou Hosp, Hematol Dept, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece.;CERTH, Inst Appl Biosci, Thessaloniki, Greece..
    An Immunogenetic Signature of Ongoing Antigen Interactions in Splenic Marginal Zone Lymphoma Expressing IGHV1-2*04 Receptors2016In: Clinical Cancer Research, ISSN 1078-0432, E-ISSN 1557-3265, Vol. 22, no 8, p. 2032-2040Article in journal (Refereed)
    Abstract [en]

    Purpose: Prompted by the extensive biases in the immunoglobulin (IG) gene repertoire of splenic marginal-zone lymphoma (SMZL), supporting antigen selection in SMZL ontogeny, we sought to investigate whether antigen involvement is also relevant post-transformation. Experimental Design: We conducted a large-scale subcloning study of the IG rearrangements of 40 SMZL cases aimed at assessing intraclonal diversification (ID) due to ongoing somatic hypermutation (SHM). Results: ID was identified in 17 of 21 (81%) rearrangements using the immunoglobulin heavy variable (IGHV) 1-2*04 gene versus 8 of 19 (40%) rearrangements utilizing other IGHV genes (P = 0.001). ID was also evident in most analyzed IG light chain gene rearrangements, albeit was more limited compared with IG heavy chains. Identical sequence changes were shared by subclones from different patients utilizing the IGHV1-2*04 gene, confirming restricted ongoing SHM profiles. Non-IGHV1-2*04 cases displayed both a lower number of ongoing SHMs and a lack of shared mutations (per group of cases utilizing the same IGHV gene). Conclusions: These findings support ongoing antigen involvement in a sizable portion of SMZL and further argue that IGHV1-2*04 SMZL may represent a distinct molecular subtype of the disease.

  • 21.
    Blanco, G.
    et al.
    Hosp del Mar, Inst Hosp Mar Invest Med IMIM, Grp Recerca Translac Neoplasies Hematol, Lab Citol Hematol,Serv Patol,Lab Citogenet Mol, Barcelona, Spain..
    Puiggros, A.
    Hosp del Mar, Inst Hosp Mar Invest Med IMIM, Grp Recerca Translac Neoplasies Hematol, Lab Citol Hematol,Serv Patol,Lab Citogenet Mol, Barcelona, Spain..
    Baliakas, Panagiotis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Athanasiadou, A.
    G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    Garcia-Malo, M. D.
    Hosp Univ Morales Meseguer, Serv Hematol, Murcia, Spain..
    Collado, R.
    Consorcio Hosp Gen Univ, Serv Hematol, Valencia, Spain..
    Xochelli, A.
    CERTH, Inst Appl Biosci, Thessaloniki, Greece..
    Rodriguez-Rivera, M.
    Hosp del Mar, Inst Hosp Mar Invest Med IMIM, Grp Recerca Translac Neoplasies Hematol, Lab Citol Hematol,Serv Patol,Lab Citogenet Mol, Barcelona, Spain..
    Ortega, M.
    Hosp Valle De Hebron, Lab Citogenet, Barcelona, Spain.;Hosp Valle De Hebron, Serv Hematol, Barcelona, Spain..
    Calasanz, M. J.
    Univ Navarra, Dept Genet, Serv Citogenet, Pamplona, Spain..
    Luno, E.
    Hosp Univ Cent Asturias, Serv Hematol, Oviedo, Spain..
    Vargas, M. T.
    Hosp Univ Virgen de la Macarena, Seville, Spain..
    Grau, J.
    Univ Autonoma Barcelona, Inst Recerca Leucemia Josep Carreras IJC, ICO Hosp Germans Trias & Pujol, Serv Lab Hematol, Badalona, Spain..
    Martinez-Laperche, C.
    Hosp GU Gregorio Maranon, Serv Hematol, Lab Genet Hematol, Madrid, Spain.;Inst Invest Sanitaria Gregorio Maranon, Madrid, Spain..
    Valiente, A.
    Complejo Hospitalario Navarra, Serv Genet, Pamplona, Spain.;Complejo Hospitalario Navarra, Serv Hematol, Pamplona, Spain..
    Papaioannou, G.
    G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    Cervera, J.
    Hosp Univ La Fe, Unidad Genet, Valencia, Spain..
    Anagnostopoulos, A.
    G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    Pinan, M. A.
    Hosp Cruces, Serv Hematol, Bilbao, Spain..
    Stalika, E.
    CERTH, Inst Appl Biosci, Thessaloniki, Greece..
    Hernandez-Rivas, J. M.
    Univ Salamanca, Hosp Univ Salamanca, Ctr Invest Canc, IBSAL,IBMCC,CSIC,Serv Hematol, Salamanca, Spain..
    Batlle, A.
    Hosp Univ Marques de Valdecilla, Serv Hematol, Santander, Spain..
    Salido, M.
    Hosp del Mar, Inst Hosp Mar Invest Med IMIM, Grp Recerca Translac Neoplasies Hematol, Lab Citol Hematol,Serv Patol,Lab Citogenet Mol, Barcelona, Spain..
    Ortuno, F.
    Hosp Univ Morales Meseguer, Serv Hematol, Murcia, Spain..
    Melero, C.
    Hosp del Mar, Inst Hosp Mar Invest Med IMIM, Grp Recerca Translac Neoplasies Hematol, Lab Citol Hematol,Serv Patol,Lab Citogenet Mol, Barcelona, Spain..
    Robles, D.
    Hosp Txagorritxu, Serv Hematol, Vitoria, Spain..
    Ferrer, A.
    Hosp del Mar, Inst Hosp Mar Invest Med IMIM, Grp Recerca Translac Neoplasies Hematol, Lab Citol Hematol,Serv Patol,Lab Citogenet Mol, Barcelona, Spain..
    Ivars, D.
    Consorcio Hosp Gen Univ, Serv Hematol, Valencia, Spain..
    Rodriguez, A.
    Hosp Univ Virgen de la Macarena, Seville, Spain..
    Gonzalez, M.
    Univ Salamanca, Hosp Univ Salamanca, Ctr Invest Canc, IBSAL,IBMCC,CSIC,Serv Hematol, Salamanca, Spain..
    Bosch, F.
    Hosp Valle De Hebron, Lab Citogenet, Barcelona, Spain.;Hosp Valle De Hebron, Serv Hematol, Barcelona, Spain..
    Abrisqueta, P.
    Hosp Valle De Hebron, Lab Citogenet, Barcelona, Spain.;Hosp Valle De Hebron, Serv Hematol, Barcelona, Spain..
    Stamatopoulos, K.
    G Papanicolaou Hosp, Inst Appl Biosci, CERTH, Dept Hematol, Thessaloniki, Greece.;G Papanicolaou Hosp, Inst Appl Biosci, CERTH, HCT Unit, Thessaloniki, Greece..
    Espinet, B.
    Hosp del Mar, Inst Hosp Mar Invest Med IMIM, Grp Recerca Translac Neoplasies Hematol, Lab Citol Hematol,Serv Patol,Lab Citogenet Mol, Barcelona, Spain..
    Chromosome 8 Abnormalities Are Associated With An Even Worse Outcome And Karyotype Complexity In Patients With Chronic Lymphocytic Leukemia And Tp53 Aberrations2016In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 101, p. 229-230Article in journal (Other academic)
  • 22.
    Blanco, Gonzalo
    et al.
    Hosp del Mar, Serv Patol, Lab Citol Hematol, Lab Citogenet Mol, Barcelona, Spain.;Hosp del Mar, IMIM, Canc Res Programme, Grp Recerca Translac Neoplasies Hematol, Barcelona, Spain.;Univ Pompeu Fabra, Dept Expt & Hlth Sci, Barcelona, Spain..
    Puiggros, Anna
    Hosp del Mar, Serv Patol, Lab Citol Hematol, Lab Citogenet Mol, Barcelona, Spain.;Hosp del Mar, IMIM, Canc Res Programme, Grp Recerca Translac Neoplasies Hematol, Barcelona, Spain..
    Baliakas, Panagiotis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Athanasiadou, Anastasia
    G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    Garcia-Malo, MaDolores
    Hosp Univ Morales Meseguer, Serv Hematol, Murcia, Spain..
    Collado, Rosa
    Consorcio Hosp Gen Univ, Serv Hematol, Valencia, Spain..
    Xochelli, Aliki
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Rodriguez-Rivera, Maria
    Hosp del Mar, Serv Patol, Lab Citol Hematol, Lab Citogenet Mol, Barcelona, Spain.;Hosp del Mar, IMIM, Canc Res Programme, Grp Recerca Translac Neoplasies Hematol, Barcelona, Spain..
    Ortega, Margarita
    Hosp Valle De Hebron, Lab Citogenet, Barcelona, Spain.;Hosp Valle De Hebron, Serv Hematol, Barcelona, Spain..
    Jose Calasanz, Ma
    Univ Navarra, Dept Genet, Serv Citogenet, Pamplona, Spain..
    Luno, Elisa
    Hosp Univ Cent Asturias, Serv Hematol, Oviedo, Spain..
    Vargas, MaTeresa
    Hosp Univ Virgen del Rocio, Inst Biomed Sevilla IBIS, UGC Hematol, Seville, Spain..
    Grau, Javier
    Univ Autonoma Barcelona, Inst Recerca Leucemia Josep Carreras IJC, ICO Hosp Germans Trias & Pujol, Serv Hematol, Badalona, Spain..
    Martinez-Laperche, Carolina
    Hosp GU Gregorio Maranon, Inst Invest Sanitaria Gregorio Maranon, Serv Hematol, Lab Genet Hematol, Madrid, Spain..
    Valiente, Alberto
    Complejo Hospitalario Navarra, Serv Genet & Hematol, Pamplona, Spain..
    Cervera, Jose
    Hosp Univ La Fe, Unidad Genet, Valencia, Spain..
    Anagnostopoulos, Achilles
    G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    Gimeno, Eva
    Hosp del Mar, Serv Hematol, Barcelona, Spain..
    Abella, Eugenia
    Hosp del Mar, Serv Hematol, Barcelona, Spain..
    Stalika, Evangelia
    CERTH, Inst Appl Biosci, Thessaloniki, Greece..
    Ma Hernandez-Rivas, Jesus
    Univ Salamanca, Hosp Univ Salamanca, Ctr Invest Canc, CSIC,Serv Hematol,IBSAL,IBMCC, Salamanca, Spain..
    Jose Ortuno, Francisco
    Hosp Univ Morales Meseguer, Serv Hematol, Murcia, Spain..
    Robles, Diego
    Hosp Txagorritxu, Serv Hematol, Vitoria, Spain..
    Ferrer, Ana
    Hosp del Mar, Serv Patol, Lab Citol Hematol, Lab Citogenet Mol, Barcelona, Spain.;Hosp del Mar, IMIM, Canc Res Programme, Grp Recerca Translac Neoplasies Hematol, Barcelona, Spain..
    Ivars, David
    Consorcio Hosp Gen Univ, Serv Hematol, Valencia, Spain..
    Gonzalez, Marcos
    Univ Salamanca, Hosp Univ Salamanca, Ctr Invest Canc, CSIC,Serv Hematol,IBSAL,IBMCC, Salamanca, Spain..
    Bosch, Francesc
    Hosp Valle De Hebron, Lab Citogenet, Barcelona, Spain.;Hosp Valle De Hebron, Serv Hematol, Barcelona, Spain..
    Abrisqueta, Pau
    Hosp Valle De Hebron, Lab Citogenet, Barcelona, Spain.;Hosp Valle De Hebron, Serv Hematol, Barcelona, Spain..
    Stamatopoulos, Kostas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab. G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece.;CERTH, Inst Appl Biosci, Thessaloniki, Greece..
    Espinet, Blanca
    Hosp del Mar, Serv Patol, Lab Citol Hematol, Lab Citogenet Mol, Barcelona, Spain.;Hosp del Mar, IMIM, Canc Res Programme, Grp Recerca Translac Neoplasies Hematol, Barcelona, Spain..
    Karyotypic complexity rather than chromosome 8 abnormalities aggravates the outcome of chronic lymphocytic leukemia patients with TP53 aberrations2016In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 7, no 49, p. 80916-80924Article in journal (Refereed)
    Abstract [en]

    Patients with chronic lymphocytic leukemia (CLL) harboring TP53 aberrations (TP53abs; chromosome 17p deletion and/or TP53 mutation) exhibit an unfavorable clinical outcome. Chromosome 8 abnormalities, namely losses of 8p (8p-) and gains of 8q (8q+) have been suggested to aggravate the outcome of patients with TP53abs. However, the reported series were small, thus hindering definitive conclusions. To gain insight into this issue, we assessed a series of 101 CLL patients harboring TP53 disruption. The frequency of 8p- and 8q+ was 14.7% and 17.8% respectively. Both were associated with a significantly (P < 0.05) higher incidence of a complex karyotype (CK, >= 3 abnormalities) detected by chromosome banding analysis (CBA) compared to cases with normal 8p (N-8p) and 8q (N-8q), respectively. In univariate analysis for 10- year overall survival (OS), 8p- (P = 0.002), 8q+ (P = 0.012) and CK (P = 0.009) were associated with shorter OS. However, in multivariate analysis only CK (HR = 2.47, P = 0.027) maintained independent significance, being associated with a dismal outcome regardless of chromosome 8 abnormalities. In conclusion, our results highlight the association of chromosome 8 abnormalities with CK amongst CLL patients with TP53abs, while also revealing that CK can further aggravate the prognosis of this aggressive subgroup.

  • 23.
    Bystry, Vojtech
    et al.
    Masaryk Univ, CEITEC Cent European Inst Technol, Brno, Czech Republic..
    Agathangelidis, Andreas
    IRCCS San Raffaele Sci Inst, Div Mol Oncol, Milan, Italy.;IRCCS San Raffaele Sci Inst, Dept Oncohematol, Milan, Italy.;Univ Vita Salute San Raffaele, Milan, Italy..
    Bikos, Vasilis
    Masaryk Univ, CEITEC Cent European Inst Technol, Brno, Czech Republic..
    Sutton, Lesley Ann
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Baliakas, Panagiotis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Hadzidimitriou, Anastasia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Ctr Res & Technol Hellas, Inst Appl Biosci, Thessaloniki, Greece..
    Stamatopoulos, Kostas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Ctr Res & Technol Hellas, Inst Appl Biosci, Thessaloniki, Greece..
    Darzentas, Nikos
    Masaryk Univ, CEITEC Cent European Inst Technol, Brno, Czech Republic..
    ARResT/AssignSubsets: a novel application for robust subclassification of chronic lymphocytic leukemia based on B cell receptor IG stereotypy2015In: Bioinformatics, ISSN 1367-4803, E-ISSN 1367-4811, Vol. 31, no 23, p. 3844-3846Article in journal (Refereed)
    Abstract [en]

    Motivation: An ever-increasing body of evidence supports the importance of B cell receptor immunoglobulin (BcR IG) sequence restriction, alias stereotypy, in chronic lymphocytic leukemia (CLL). This phenomenon accounts for similar to 30% of studied cases, one in eight of which belong to major subsets, and extends beyond restricted sequence patterns to shared biologic and clinical characteristics and, generally, outcome. Thus, the robust assignment of new cases to major CLL subsets is a critical, and yet unmet, requirement. Results: We introduce a novel application, ARResT/AssignSubsets, which enables the robust assignment of BcR IG sequences from CLL patients to major stereotyped subsets. ARResT/AssignSubsets uniquely combines expert immunogenetic sequence annotation from IMGT/V-QUEST with curation to safeguard quality, statistical modeling of sequence features from more than 7500 CLL patients, and results from multiple perspectives to allow for both objective and subjective assessment. We validated our approach on the learning set, and evaluated its real-world applicability on a new representative dataset comprising 459 sequences from a single institution.

  • 24.
    Chatzilari, Elisavet
    et al.
    CERTH, Inst Informat Technol, Thessaloniki, Greece..
    Baliakas, Panagiotis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Xochelli, Aliki
    Ctr Res & Technol Hellas, Thessaloniki, Greece.;CERTH, Inst Appl Biosci, Thessaloniki, Greece..
    Maronidis, Anastasios
    CERTH, Inst Informat Technol, Thessaloniki, Greece..
    Vardi, Anna
    CERTH, Inst Appl Biosci, Thessaloniki, Greece.;G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    Mattsson, Mattias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Larsson, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Douka, Vassiliki
    G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    Iskas, Michail
    George Papanicolaou Gen Hosp, Hematol BMT Unit, Thessaloniki, Greece..
    Karavalakis, George
    G Papanicolaou Hosp, BMT Unit, Dept Hematol, Thessaloniki, Greece..
    Papalexandri, Apostolia
    G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    Niemann, Carsten
    Rigshosp, Dept Hematol, DK-2100 Copenhagen, Denmark..
    Montillo, Marco
    Osped Niguarda Ca Granda, Niguarda Canc Ctr, Mol Pathol Unit, Milan, Italy.;Osped Niguarda Ca Granda, Niguarda Canc Ctr, Dept Haematol, Milan, Italy..
    Anagnostopoulos, Achilles
    G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    Oscier, David
    Royal Bournemouth Hosp, Dept Haematol, Bournemouth, Dorset, England..
    Pospisilova, Sarka
    Masaryk Univ, Cent European Inst Technol, Brno, Czech Republic.;Univ Hosp Brno, Brno, Czech Republic..
    Davi, Frederic
    Hop La Pitie Salpetriere, Dept Biol Hematol, Paris, France.;Univ Paris 06, Paris, France..
    Stavroyianni, Niki
    G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    Ghia, Paolo
    IRCCS San Raffaele Sci Inst, Div Expt Oncol, Milan, Italy.;IRCCS San Raffaele Sci Inst, Dept Oncohematol, Milan, Italy..
    Hadzidimitriou, Anastasia
    CERTH, Inst Appl Biosci, Thessaloniki, Greece..
    Rosenquist, Richard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Nikolopoulos, Spiros
    CERTH, Inst Informat Technol, Thessaloniki, Greece..
    Stamatopoulos, Kostas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Kompatsiaris, Yannis
    CERTH, Inst Informat Technol, Thessaloniki, Greece..
    Personalized Modeling of Disease Evolution in CLL: Does Statistical Significance Translate into Predictive Accuracy?2015In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 126, no 23Article in journal (Other academic)
  • 25.
    Chatzilari, Elisavet
    et al.
    CERTH, Inst Informat Technol, Thessaloniki, Greece..
    Baliakas, Panagiotis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Xochelli, Aliki
    Ctr Res & Technol Hellas, Thessaloniki, Greece.;CERTH, Inst Appl Biosci, Thessaloniki, Greece..
    Maronidis, Anastasios
    CERTH, Inst Informat Technol, Thessaloniki, Greece..
    Vardi, Anna
    CERTH, Inst Appl Biosci, Thessaloniki, Greece.;G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    Mattsson, Mattias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Larsson, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Douka, Vassiliki
    G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    Iskas, Michail
    George Papanicolaou Gen Hosp, Hematol BMT Unit, Thessaloniki, Greece..
    Karavalakis, George
    G Papanicolaou Hosp, BMT Unit, Dept Hematol, Thessaloniki, Greece..
    Papalexandri, Apostolia
    G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    Niemann, Carsten
    Rigshosp, Dept Hematol, DK-2100 Copenhagen, Denmark..
    Montillo, Marco
    Osped Niguarda Ca Granda, Niguarda Canc Ctr, Mol Pathol Unit, Milan, Italy.;Osped Niguarda Ca Granda, Niguarda Canc Ctr, Dept Haematol, Milan, Italy..
    Anagnostopoulos, Achilles
    G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    Oscier, David
    Royal Bournemouth Hosp, Dept Haematol, Bournemouth, Dorset, England..
    Pospisilova, Sarka
    Masaryk Univ, Cent European Inst Technol, Brno, Czech Republic.;Univ Hosp Brno, Brno, Czech Republic..
    Davi, Frederic
    Hop La Pitie Salpetriere, Dept Biol Hematol, Paris, France.;Univ Paris 06, Paris, France..
    Stavroyianni, Niki
    G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    Ghia, Paolo
    IRCCS San Raffaele Sci Inst, Div Expt Oncol, Milan, Italy.;IRCCS San Raffaele Sci Inst, Dept Oncohematol, Milan, Italy..
    Hadzidimitriou, Anastasia
    CERTH, Inst Appl Biosci, Thessaloniki, Greece..
    Rosenquist, Richard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Nikolopoulos, Spiros
    CERTH, Inst Informat Technol, Thessaloniki, Greece..
    Stamatopoulos, Kostas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. CERTH, Inst Appl Biosci, Thessaloniki, Greece..
    Kompatsiaris, Yannis
    CERTH, Inst Informat Technol, Thessaloniki, Greece..
    Personalized Modeling of Disease Evolution in CLL: Does Statistical Significance Translate into Predictive Accuracy?2015In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 126, no 23Article in journal (Other academic)
  • 26.
    Gemenetzi, Katerina
    et al.
    Ctr Res & Technol Hellas, Inst Appl Biosci, Thessaloniki, Greece..
    Galigalidou, Chrysi
    Ctr Res & Technol Hellas, Inst Appl Biosci, Thessaloniki, Greece..
    Vlachonikola, Elisavet
    Ctr Res & Technol Hellas, Inst Appl Biosci, Thessaloniki 57001, Greece..
    Stalika, Evangelia
    Ctr Res & Technol Hellas, Inst Appl Biosci, Thessaloniki 57001, Greece.; G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece.; G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    Xochelli, Aliki
    Ctr Res & Technol Hellas, Inst Appl Biosci, Thessaloniki , Greece.; G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    Baliakas, Panagiotis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Karypidou, Maria
    G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    Touloumenidou, Tasoula
    G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    Minga, Evangelia
    Ctr Res & Technol Hellas, Inst Appl Biosci, Thessaloniki 57001, Greece..
    Douka, Vasiliki
    G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    Iskas, Michalis
    G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    Athanasiadou, Anastasia
    G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    Makris, Antonios
    Ctr Res & Technol Hellas, Inst Appl Biosci, Thessaloniki , Greece..
    Stavroyianni, Niki
    G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    Anagnostopoulos, Achilles
    G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    Hadzidimitriou, Anastasia
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Ctr Res & Technol Hellas, Inst Appl Biosci, Thessaloniki 57001, Greece..
    Stamatopoulos, Kostas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab. Ctr Res & Technol Hellas, Inst Appl Biosci, Thessaloniki, Greece..
    Tp53 gene p72R polymorphism in chronic lymphocytic leukemia: incidence and clinical significance amongst cases with unmutated immunoglobulin receptors2017In: Leukemia and Lymphoma, ISSN 1042-8194, E-ISSN 1029-2403, Vol. 58, no 3, p. 726-728Article in journal (Refereed)
  • 27.
    Gonzalo, Blanco
    et al.
    Hosp del Mar, Serv Patol, Lab Citol Hematol, Lab Citogenet Mol, Barcelona, Spain.;Inst Hosp Mar Invest Med IMIM, Programa Recerca Canc, Grp Recerca Translac Neoplasies Hematol, Barcelona, Spain.;Univ Pompeu Fabra, Dept Ciencias Expt & Salud, Barcelona, Spain..
    Anna, Puiggros
    Hosp del Mar, Serv Patol, Lab Citol Hematol, Lab Citogenet Mol, Barcelona, Spain.;Inst Hosp Mar Invest Med IMIM, Programa Recerca Canc, Grp Recerca Translac Neoplasies Hematol, Barcelona, Spain..
    Baliakas, Panagiotis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Anastasia, Athanasiadou
    G Papanicolaou Hosp, Hematol Dept, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    Ma Dolores, Garcia-Malo
    Hosp Univ Morales Meseguer, Serv Hematol, Murcia, Spain..
    Rosa, Collado
    Consorcio Hosp Gen Univ, Serv Hematol, Valencia, Spain..
    Aliki, Xochelli
    CERTH, Inst Appl Biosci, Thessaloniki, Greece..
    Maria, Rodriguez-Rivera
    Hosp del Mar, Serv Patol, Lab Citol Hematol, Lab Citogenet Mol, Barcelona, Spain.;Inst Hosp Mar Invest Med IMIM, Programa Recerca Canc, Grp Recerca Translac Neoplasies Hematol, Barcelona, Spain..
    Margarita, Ortega
    Hosp Valle De Hebron, Lab Citogenet, Barcelona, Spain.;Hosp Valle De Hebron, Serv Hematol, Barcelona, Spain..
    Ma Jose, Calasanz
    Univ Navarra, Dept Genet, Serv Citogenet, Pamplona, Spain..
    Elisa, Luno
    Hosp Univ Cent Asturias, Serv Hematol, Oviedo, Spain..
    Ma Teresa, Vargas
    Hosp Univ Virgen de la Macarena, Seville, Spain.;Univ Autonoma Barcelona, Serv Lab Hematol, ICO Hosp Germans Trias & Pujol, Inst Recerca Leucemia Josep Carreras IJC, Badalona, Spain..
    Javier, Grau
    Carolina, Martinez-Laperche
    Hosp Gen Univ Gregorio Maranon, Serv Hematol, Lab Genet Hematol, Madrid, Spain.;Inst Invest Sanitaria Gregorio Maranon, Madrid, Spain..
    Alberto, Valiente
    Complejo Hosp Navarra, Serv Genet Hematol, Pamplona, Spain..
    Jose, Cervera
    Hosp Univ La Fe, Unidad Genet, Valencia, Spain..
    Jesus Ma, Hernandez-Rivas
    Univ Salamanca, Serv Hematol, Hosp Univ Salamanca, IBSAL,IBMCC,Ctr Invest Canc,CSIC, Salamanca, Spain..
    Eva, Gimeno
    Hosp del Mar, Serv Hematol, Barcelona, Spain..
    Francisco Jose, Ortuno
    Hosp Univ Morales Meseguer, Serv Hematol, Murcia, Spain..
    Ana, Ferrer
    Hosp del Mar, Serv Patol, Lab Citol Hematol, Lab Citogenet Mol, Barcelona, Spain.;Inst Hosp Mar Invest Med IMIM, Programa Recerca Canc, Grp Recerca Translac Neoplasies Hematol, Barcelona, Spain..
    Marcos, Gonzalez
    Univ Salamanca, Serv Hematol, Hosp Univ Salamanca, IBSAL,IBMCC,Ctr Invest Canc,CSIC, Salamanca, Spain..
    Francesc, Bosch
    Hosp Valle De Hebron, Lab Citogenet, Barcelona, Spain.;Hosp Valle De Hebron, Serv Hematol, Barcelona, Spain..
    Pau, Abrisqueta
    Hosp Valle De Hebron, Lab Citogenet, Barcelona, Spain.;Hosp Valle De Hebron, Serv Hematol, Barcelona, Spain..
    Kostas, Stamatopoulos
    CERTH, Inst Appl Biosci, G Papanicolaou Hosp, Hematol Dept, Thessaloniki, Greece.;CERTH, Inst Appl Biosci, G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    Blanca, Espinet
    Hosp del Mar, Serv Patol, Lab Citol Hematol, Lab Citogenet Mol, Barcelona, Spain.;Inst Hosp Mar Invest Med IMIM, Programa Recerca Canc, Grp Recerca Translac Neoplasies Hematol, Barcelona, Spain..
    Gains of 8q and losses of 8p is associated with the presence of complex karyotype improving prognosis in patients with lymphatic leukemia chronic and alterations of tp532016In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 101, no Suppl. 4, p. 196-197Article in journal (Other academic)
  • 28. Iskas, M.
    et al.
    Papaioannou, G.
    Baliakas, Panagiotis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Hematology and Immunology.
    Gaitatzi, M.
    Lazarou, Z.
    Stalika, E.
    Stamatopoulos, K.
    Anagnostopoulos, A.
    Athanasiadou, A.
    Cytogenetic Evolution Patterns in Chronic Lymphocytic Leukemia2014In: Haematologica (online), ISSN 0390-6078, E-ISSN 1592-8721, Vol. 99, p. 314-314Article in journal (Other academic)
  • 29.
    Ljungström, Viktor
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Cortese, Diego
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Young, Emma
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Pandzic, Tatjana
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Mansouri, Larry
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Plevova, Karla
    Ntoufa, Stavroula
    Baliakas, Panagiotis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Clifford, Ruth
    Sutton, Lesley-Ann
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Blakemore, Stuart
    Stavroyianni, Niki
    Agathangelidis, Andreas
    Rossi, Davide
    Höglund, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Kotaskova, Jana
    Juliusson, Gunnar
    Belessi, Chrysoula
    Chiorazzi, Nicholas
    Panagiotidis, Panagiotis
    Langerak, Anton W
    Smedby, Karin E
    Oscier, David
    Gaidano, Gianluca
    Schuh, Anna
    Davi, Frederic
    Pott, Christiane
    Strefford, Jonathan C
    Trentin, Livio
    Pospisilova, Sarka
    Ghia, Paolo
    Stamatopoulos, Kostas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Sjöblom, Tobias
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Rosenquist, Richard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Whole-exome sequencing in relapsing chronic lymphocytic leukemia: clinical impact of recurrent RPS15 mutations2016In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 127, no 8, p. 1007-1016Article in journal (Refereed)
    Abstract [en]

    Fludarabine, cyclophosphamide and rituximab (FCR) is first-line treatment for medically fit chronic lymphocytic leukemia (CLL) patients, however despite good response rates many patients eventually relapse. Whilst recent high-throughput studies have identified novel recurrent genetic lesions in adverse-prognostic CLL, the mechanisms leading to relapse after FCR therapy are not completely understood. To gain insight into this issue, we performed whole-exome sequencing of sequential samples from 41 CLL patients who were uniformly treated with FCR but relapsed after a median of 2 years. In addition to mutations with known adverse-prognostic impact (TP53, NOTCH1, ATM, SF3B1, NFKBIE, BIRC3) a large proportion of cases (19.5%) harbored mutations in RPS15, a gene encoding a component of the 40S ribosomal subunit. Extended screening, totaling 1119 patients, supported a role for RPS15 mutations in aggressive CLL, with one-third of RPS15-mutant cases also carrying TP53 aberrations. In most cases selection of dominant, relapse-specific subclones was observed over time. However, RPS15 mutations were clonal prior to treatment and remained stable at relapse. Notably, all RPS15 mutations represented somatic missense variants and resided within a 7 amino-acid evolutionarily conserved region. We confirmed the recently postulated direct interaction between RPS15 and MDM2/MDMX and transient expression of mutant RPS15 revealed defective regulation of endogenous p53 compared to wildtype RPS15. In summary, we provide novel insights into the heterogeneous genetic landscape of CLL relapsing after FCR treatment and highlight a novel mechanism underlying clinical aggressiveness involving a mutated ribosomal protein, potentially representing an early genetic lesion in CLL pathobiology.

  • 30. Malcikova, Jitka
    et al.
    Stalika, Evangelia
    Davis, Zadie
    Plevova, Karla
    Trbusek, Martin
    Mansouri, Larry
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Hematology and Immunology.
    Scarfo, Lydia
    Baliakas, Panagiotis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Hematology and Immunology.
    Gardiner, Anne
    Sutton, Lesley-Ann
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Francova, Hana Skuhrova
    Agathangelidis, Andreas
    Anagnostopoulos, Achilles
    Tracy, Ian
    Makris, Antonis
    Smardova, Jana
    Ghia, Paolo
    Belessi, Chrysoula
    Gonzalez, David
    Rosenquist, Richard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Hematology and Immunology.
    Oscier, David
    Pospisilova, Sarka
    Stamatopoulos, Kostas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    The frequency of TP53 gene defects differs between chronic lymphocytic leukaemia subgroups harbouring distinct antigen receptors2014In: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 166, no 4, p. 621-625Article in journal (Refereed)
  • 31.
    Navrkalova, Veronika
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Masaryk Univ, Cent European Inst Technol, Brno, Czech Republic.;Univ Hosp Brno, Dept Internal Med Hematol & Oncol, Brno, Czech Republic..
    Young, Emma
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Baliakas, Panagiotis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Radova, Lenka
    Masaryk Univ, Cent European Inst Technol, Brno, Czech Republic..
    Plevova, Karla
    Masaryk Univ, Cent European Inst Technol, Brno, Czech Republic.;Univ Hosp Brno, Dept Internal Med Hematol & Oncol, Brno, Czech Republic.;Masaryk Univ, Fac Med, Brno, Czech Republic..
    Sutton, Lesley-Ann
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Mansouri, Larry
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Ljungström, Viktor
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Ntoufa, Stavroula
    CERTH, Inst Appl Biosci, Thessaloniki, Greece..
    Davis, Zadie
    Royal Bournemouth Hosp, Dept Mol Pathol, Bournemouth, Dorset, England..
    Juliusson, Gunnar
    Lund Univ, Dept Lab Med, Stem Cell Ctr, Hematol & Transplantat, Lund, Sweden..
    Smedby, Karin E.
    Karolinska Inst, Dept Med, Clin Epidemiol Unit, Stockholm, Sweden..
    Belessi, Chrysoula
    Nikea Gen Hosp, Dept Hematol, Piraeus, Greece..
    Panagiotidis, Panagiotis
    Univ Athens, Dept Propaedeut Med 1, Athens, Greece..
    Davi, Frederic
    Hop La Pitie Salpetriere, Dept Biol Hematol, Paris, France.;Univ Paris 06, Paris, France..
    Langerak, Anton W.
    Erasmus Univ, Dept Immunol, Med Ctr, NL-3000 DR Rotterdam, Netherlands..
    Ghia, Paolo
    IRCCS San Raffaele Sci Inst, Div Expt Oncol, Milan, Italy.;IRCCS San Raffaele Sci Inst, Dept Oncohematol, Milan, Italy..
    Strefford, Jonathan C.
    Univ Southampton, Canc Sci Unit, Southampton, Hants, England..
    Oscier, David G.
    Royal Bournemouth Hosp, Dept Mol Pathol, Bournemouth, Dorset, England..
    Stamatopoulos, Kostas
    CERTH, Inst Appl Biosci, Thessaloniki, Greece..
    Pospisilova, Sarka
    Masaryk Univ, Cent European Inst Technol, Brno, Czech Republic.;Univ Hosp Brno, Dept Internal Med Hematol & Oncol, Brno, Czech Republic..
    Rosenquist, Richard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Trbusek, Martin
    Masaryk Univ, Cent European Inst Technol, Brno, Czech Republic.;Univ Hosp Brno, Dept Internal Med Hematol & Oncol, Brno, Czech Republic.;Masaryk Univ, Fac Med, Brno, Czech Republic..
    ATM Mutations in Major Stereotyped CLL Subsets: Enrichment in Subset #2 is Associated with Unfavourable Outcome2015In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 126, no 23Article in journal (Other academic)
  • 32.
    Navrkalova, Veronika
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab. Univ Hosp Brno, Dept Internal Med Hematol & Oncol, Brno, Czech Republic.;Masaryk Univ, Fac Med, Brno, Czech Republic.;Masaryk Univ, CEITEC Cent European Inst Technol, Dept Mol Med, Brno, Czech Republic..
    Young, Emma
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Baliakas, Panagiotis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Radova, Lenka
    Masaryk Univ, CEITEC Cent European Inst Technol, Dept Mol Med, Brno, Czech Republic..
    Sutton, Lesley-Ann
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Plevova, Karla
    Univ Hosp Brno, Dept Internal Med Hematol & Oncol, Brno, Czech Republic.;Masaryk Univ, Fac Med, Brno, Czech Republic.;Masaryk Univ, CEITEC Cent European Inst Technol, Dept Mol Med, Brno, Czech Republic..
    Mansouri, Larry
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Ljungström, Viktor
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Ntoufa, Stavroula
    CERTH, Inst Appl Biosci, Thessaloniki, Greece..
    Davis, Zadie
    Royal Bournemouth Hosp, Dept Mol Pathol, Bournemouth, Dorset, England..
    Juliusson, Gunnar
    Lund Univ, Stem Cell Ctr, Hematol & Transplantat, Dept Lab Med, Lund, Sweden..
    Smedby, Karin E.
    Karolinska Inst, Clin Epidemiol Unit, Dept Med Solna, Stockholm, Sweden..
    Belessi, Chrysoula
    Gen Hosp Nikea, Dept Hematol, Piraeus, Greece..
    Panagiotidis, Panagiotis
    Univ Athens, Sch Med, Dept Propaedeut Med 1, Athens, Greece..
    Touloumenidou, Tasoula
    CERTH, Inst Appl Biosci, Thessaloniki, Greece.;G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    Davi, Frederic
    Hosp Pitie Salpetriere, Hematol Lab, Paris, France.;Univ Paris 06, Paris, France..
    Langerak, Anton W.
    Univ Med Ctr Rotterdam, Erasmus MC, Dept Immunol, Rotterdam, Netherlands..
    Ghia, Paolo
    IRCCS San Raffaele Sci Inst, Div Expt Oncol, Milan, Italy.;IRCCS San Raffaele Sci Inst, Dept Oncohematol, Milan, Italy..
    Strefford, Jonathan C.
    Univ Southampton, Fac Med, Canc Sci, Southampton, Hants, England..
    Oscier, David
    Royal Bournemouth Hosp, Dept Mol Pathol, Bournemouth, Dorset, England..
    Mayer, Jiri
    Univ Hosp Brno, Dept Internal Med Hematol & Oncol, Brno, Czech Republic.;Masaryk Univ, Fac Med, Brno, Czech Republic..
    Stamatopoulos, Kostas
    CERTH, Inst Appl Biosci, Thessaloniki, Greece..
    Pospisilova, Sarka
    Univ Hosp Brno, Dept Internal Med Hematol & Oncol, Brno, Czech Republic.;Masaryk Univ, Fac Med, Brno, Czech Republic.;Masaryk Univ, CEITEC Cent European Inst Technol, Dept Mol Med, Brno, Czech Republic..
    Rosenquist, Richard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Trbusek, Martin
    Univ Hosp Brno, Dept Internal Med Hematol & Oncol, Brno, Czech Republic.;Masaryk Univ, Fac Med, Brno, Czech Republic..
    ATM mutations in major stereotyped subsets of chronic lymphocytic leukemia: enrichment in subset #2 is associated with markedly short telomeres2016In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 101, no 9, article id e372Article in journal (Refereed)
  • 33.
    Noerenberg, Daniel
    et al.
    Univ Hosp Rudolf Virchow, Charite, Dept Hematol Oncol & Tumor Immunol, Berlin, Germany..
    Young, Emma
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Ljungström, Viktor
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Mansouri, Larry
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Plevova, Karla
    Masaryk Univ, Cent European Inst Technol, Brno, Czech Republic..
    Baliakas, Panagiotis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Blakemore, Stuart
    Univ Southampton, Fac Med, Canc Sci, Southampton SO9 5NH, Hants, England..
    Rossi, Davide
    Amedeo Avogadro Univ Eastern Piedmont, Dept Translat Med, Div Hematol, Novara, Italy..
    Clifford, Ruth
    Univ Oxford, Mol Diagnost Ctr, Hlth Res Biomed Res Ctr, Oxford Natl Inst, Oxford, England..
    Navrkalova, Veronika
    Masaryk Univ, Cent European Inst Technol, Brno, Czech Republic..
    Sutton, Lesley-Ann
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Smedby, Karin E.
    Karolinska Inst, Clin Epidemiol Unit, Dept Med, Stockholm, Sweden..
    Juliusson, Gunnar
    Lund Univ, Stem Cell Ctr, Hematol & Transplantat, Lund, Sweden..
    Belessi, Chrysoula
    Nikea Gen Hosp, Dept Hematol, Piraeus, Greece..
    Panagiotidis, Panagiotis
    Univ Athens, Sch Med, Dept Propaedeut Med 1, GR-11527 Athens, Greece..
    Chiorazzi, Nicholas
    North Shore LIJ Hlth Syst, Feinstein Inst Med Res, Manhasset, NY USA..
    Davi, Frederic
    Hop La Pitie Salpetriere, Hematol Lab, Paris, France.;Univ Paris 06, Paris, France..
    Langerak, Anton W.
    Erasmus MC, Dept Immunol, Rotterdam, Netherlands..
    Schuh, Anna
    Univ Oxford, Mol Diagnost Ctr, Hlth Res Biomed Res Ctr, Oxford Natl Inst, Oxford, England..
    Gaidano, Gianluca
    Amedeo Avogadro Univ Eastern Piedmont, Dept Translat Med, Div Hematol, Novara, Italy..
    Strefford, Jonathan C.
    Univ Southampton, Canc Sci Unit, Southampton, Hants, England..
    Ghia, Paolo
    Univ Vita Salute San Raffaele, Div Mol Oncol, Milan, Italy.;Univ Vita Salute San Raffaele, Dept Oncol, Milan, Italy.;Ist Sci San Raffaele, Milan, Italy..
    Stamatopoulos, Kostas
    CERTH, Inst Appl Biosci, Thessaloniki, Greece..
    Pospisilova, Sarka
    Masaryk Univ, Cent European Inst Technol, Brno, Czech Republic..
    Zenz, Thorsten
    Univ Heidelberg Hosp, Dept Internal Med 5, Heidelberg, Germany.;German Consortium Translat Canc Res DKTK, Heidelberg, Germany..
    Rosenquist, Richard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Damm, Frederik
    Univ Hosp Rudolf Virchow, Charite, Dept Hematol Oncol & Tumor Immunol, Berlin, Germany..
    EGR2 Mutations in Chronic Lymphocytic Leukemia: A New Bad Player2015In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 126, no 23Article in journal (Other academic)
  • 34.
    Papakonstantinou, Nikos
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Ctr Res & Technol Hellas, Inst Appl Biosci, Thessaloniki, Greece..
    Ntoufa, Stavroula
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Ctr Res & Technol Hellas, Inst Appl Biosci, Thessaloniki, Greece..
    Chartomatsidou, Elisavet
    Ctr Res & Technol Hellas, Inst Appl Biosci, Thessaloniki, Greece..
    Kotta, Konstantia
    Ctr Res & Technol Hellas, Inst Appl Biosci, Thessaloniki, Greece..
    Agathangelidis, Andreas
    IRCCS San Raffaele Sci Inst, Div Expt Oncol, Milan, Italy.;IRCCS San Raffaele Sci Inst, Dept Oncohematol, Milan, Italy.;Univ Vita Salute San Raffaele, Milan, Italy..
    Giassafaki, Lefki
    Ctr Res & Technol Hellas, Inst Appl Biosci, Thessaloniki, Greece..
    Karamanli, Tzeni
    Ctr Res & Technol Hellas, Inst Appl Biosci, Thessaloniki, Greece..
    Bele, Panagiota
    Ctr Res & Technol Hellas, Inst Appl Biosci, Thessaloniki, Greece..
    Moysiadis, Theodoros
    Ctr Res & Technol Hellas, Inst Appl Biosci, Thessaloniki, Greece..
    Baliakas, Panagiotis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Sutton, Lesley Ann
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Stavroyianni, Niki
    G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    Anagnostopoulos, Achilles
    G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    Makris, Antonios M.
    Ctr Res & Technol Hellas, Inst Appl Biosci, Thessaloniki, Greece..
    Ghia, Paolo
    IRCCS San Raffaele Sci Inst, Div Expt Oncol, Milan, Italy.;IRCCS San Raffaele Sci Inst, Dept Oncohematol, Milan, Italy.;Univ Vita Salute San Raffaele, Milan, Italy..
    Rosenquist, Richard
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Stamatopoulos, Kostas
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Ctr Res & Technol Hellas, Inst Appl Biosci, Thessaloniki, Greece.;G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    The histone methyltransferase EZH2 as a novel prosurvival factor in clinically aggressive chronic lymphocytic leukemia2016In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 7, no 24, p. 35946-35959Article in journal (Refereed)
    Abstract [en]

    The histone methyltransferase EZH2 induces gene repression through trimethylation of histone H3 at lysine 27 (H3K27me3). EZH2 overexpression has been reported in many types of cancer and associated with poor prognosis. Here we investigated the expression and functionality of EZH2 in chronic lymphocytic leukemia (CLL). Aggressive cases with unmutated IGHV genes (U-CLL) displayed significantly higher EZH2 expression compared to indolent CLL cases with mutated IGHV genes (M-CLL); furthermore, in U-CLL EZH2 expression was upregulated with disease progression. Within U-CLL, EZH2(high) cases harbored significantly fewer (p = 0.033) TP53 gene abnormalities compared to EZH2(low) cases. EZH2(high) cases displayed high H3K27me3 levels and increased viability suggesting that EZH2 is functional and likely confers a survival advantage to CLL cells. This argument was further supported by siRNA-mediated downmodulation of EZH2 which resulted in increased apoptosis. Notably, at the intraclonal level, cell proliferation was significantly associated with EZH2 expression. Treatment of primary CLL cells with EZH2 inhibitors induced downregulation of H3K27me3 levels leading to increased cell apoptosis. In conclusion, EZH2 is overexpressed in adverse-prognosis CLL and associated with increased cell survival and proliferation. Pharmacologic inhibition of EZH2 catalytic activity promotes apoptosis, highlighting EZH2 as a novel potential therapeutic target for specific subgroups of patients with CLL.

  • 35. Psatha, Nikoleta
    et al.
    Sgouramali, Eleni
    Gkountis, Antonios
    Siametis, Athanasios
    Baliakas, Panayotis
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Constantinou, Varnavas
    Athanasiou, Evangelia
    Arsenakis, Minas
    Anagnostopoulos, Achilles
    Papayannopoulou, Thalia
    Stamatoyannopoulos, George
    Yannaki, Evangelia
    Superior Long-Term Repopulating Capacity of G-CSF+Plerixafor-Mobilized Blood: Implications for Stem Cell Gene Therapy by Studies in the Hbb(th-3) Mouse Model2014In: Human Gene Therapy Methods, ISSN 1946-6536, Vol. 25, no 6, p. 317-327Article in journal (Refereed)
    Abstract [en]

    High numbers of genetically modified hematopoietic stem cells (HSCs) equipped with enhanced engrafting potential are required for successful stem cell gene therapy. By using thalassemia as a model, we investigated the functional properties of hematopoietic stem and progenitor cells (HSPCs) from Hbb(th3)/45.2(+) mice after mobilization with G-CSF, plerixafor, or G-CSF+plerixafor and the engraftment kinetics of primed cells after competitive primary and noncompetitive secondary transplantation. G-CSF+plerixafor yielded the highest numbers of HSPCs, while G-CSF+plerixafor-mobilized Hbb(th3)/45.2(+) cells, either unmanipulated or transduced with a reporter vector, achieved faster hematologic reconstitution and higher levels of donor chimerism over all other types of mobilized cells, after competitive transplantation to B6.BoyJ/45.1(+) recipients. The engraftment benefit observed in the G-CSF+plerixafor group was attributed to the more primitive stem cell phenotype of G-CSF+plerixafor-LSK cells, characterized by higher CD150(+)/CD48 expression. Moreover, secondary G-CSF+plerixafor recipients displayed stable or even higher chimerism levels as compared with primary engrafted mice, thus maintaining or further improving engraftment levels over G-CSF- or plerixafor-secondary recipients. Plerixafor-primed cells displayed the lowest competiveness over all other mobilized cells after primary or secondary transplantation, probably because of the higher frequency of more actively proliferating LK cells. Overall, the higher HSC yields, the faster hematological recovery, and the superiority in long-term engraftment indicate G-CSF+plerixafor-mobilized blood as an optimal graft source, not only for thalassemia gene therapy, but also for stem cell gene therapy applications in general.

  • 36.
    Rosenquist, Richard
    et al.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.;UPMC Univ Paris 06, Hop Pitie Salpetriere, AP HP, Dept Hematol, Paris, France..
    Ghia, P.
    IRCCS, Ist Sci San Raffaele, Div Expt Oncol, Milan, Italy.;UPMC Univ Paris 06, Hop Pitie Salpetriere, AP HP, Dept Hematol, Paris, France..
    Hadzidimitriou, A.
    Univ Vita Salute San Raffaele, Milan, Italy..
    Sutton, Lesley Ann
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden..
    Agathangelidis, A.
    IRCCS, Ist Sci San Raffaele, Div Expt Oncol, Milan, Italy..
    Baliakas, Panagiotis
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Darzentas, N.
    Ctr Res & Technol Hellas, Inst Appl Biosci, Thessaloniki, Greece..
    Giudicelli, V.
    Masaryk Univ, CEITEC Cent European Inst Technol, Brno, Czech Republic..
    Lefranc, M-P
    Masaryk Univ, CEITEC Cent European Inst Technol, Brno, Czech Republic..
    Langerak, A. W.
    Univ Montpellier, IGH, UMR CNRS 9002, Lab ImmunoGenet Mol LIGM,IMGT, Montpellier, France..
    Belessi, C.
    Erasmus MC, Lab Med Immunol, Dept Immunol, Rotterdam, Netherlands..
    Davi, F.
    Nikea Gen Hosp, Dept Hematol, Athens, Greece.;UPMC Univ Paris 06, Hop Pitie Salpetriere, AP HP, Dept Hematol, Paris, France..
    Stamatopoulos, Kostas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab. Univ Vita Salute San Raffaele, Milan, Italy.;UPMC Univ Paris 06, Hop Pitie Salpetriere, AP HP, Dept Hematol, Paris, France..
    Immunoglobulin gene sequence analysis in chronic lymphocytic leukemia: updated ERIC recommendations2017In: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 31, no 7, p. 1477-1481Article in journal (Other academic)
  • 37. Strefford, J. C.
    et al.
    Sutton, Lesley Ann
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Hematology and Immunology.
    Baliakas, Panagiotis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Hematology and Immunology.
    Agathangelidis, A.
    Malcikova, J.
    Plevova, K.
    Scarfo, L.
    Davis, Z.
    Stalika, E.
    Cortese, Diego
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Hematology and Immunology.
    Cahill, Nicola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Pedersen, L. B.
    di Celle, P. F.
    Tzenou, T.
    Geisler, C.
    Panagiotidis, P.
    Langerak, A. W.
    Chiorazzi, N.
    Pospisilova, S.
    Oscier, D.
    Davi, F.
    Belessi, C.
    Mansouri, Larry
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Hematology and Immunology.
    Ghia, P.
    Stamatopoulos, K.
    Rosenquist, Richard Brandell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Hematology and Immunology.
    Distinct patterns of novel gene mutations in poor-prognostic stereotyped subsets of chronic lymphocytic leukemia: the case of SF3B1 and subset #22013In: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 27, no 11, p. 2196-2199Article in journal (Refereed)
    Abstract [en]

    Recent studies have revealed recurrent mutations of the NOTCH1, SF3B1 and BIRC3 genes in chronic lymphocytic leukemia (CLL), especially among aggressive, chemorefractory cases. Nevertheless, it is currently unknown whether their presence may differ in subsets of patients carrying stereotyped B-cell receptors and also exhibiting distinct prognoses. Here, we analyzed the mutation status of NOTCH1, SF3B1 and BIRC3 in three subsets with particularly poor prognosis, that is, subset # 1, # 2 and # 8, aiming to explore links between genetic aberrations and immune signaling. A remarkably higher frequency of SF3B1 mutations was revealed in subset # 2 (44%) versus subset # 1 and # 8 (4.6% and 0%, respectively; P<0.001). In contrast, the frequency of NOTCH1 mutations in subset # 2 was only 8%, lower than the frequency observed in either subset # 1 or # 8 (19% and 14%, respectively; P 0.04 for subset # 1 versus # 2). No associations were found for BIRC3 mutations that overall were rare. The apparent non-random association of certain mutations with stereotyped CLL subsets alludes to subset-biased acquisition of genomic aberrations, perhaps consistent with particular antigen/antibody interactions. These novel findings assist in unraveling specific mechanisms underlying clinical aggressiveness in poor-prognostic stereotyped subsets, with far-reaching implications for understanding their clonal evolution and implementing biologically oriented therapy.

  • 38.
    Sutton, Lesley Ann
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab. Karolinska Institute, Dept Mol Med & Surg.
    Hadzidimitriou, Anastasia
    Baliakas, Panagiotis
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Agathangelidis, Andreas
    Langerak, Anton W.
    Stilgenbauer, Stephan
    Pospisilova, Sarka
    Davis, Zadie
    Forconi, Francesco
    Davi, Frederic
    Ghia, Paolo
    Rosenquist, Richard
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.
    Stamatopoulos, Kostas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Institute of Applied Biosciences, Center for Research and Technology Hellas, Thessaloniki, Greece.
    Immunoglobulin genes in chronic lymphocytic leukemia: key to understanding the disease and improving risk stratification2017In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 102, no 6, p. 968-971Article in journal (Other academic)
  • 39.
    Sutton, Lesley-Ann
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Young, Emma
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Baliakas, Panagiotis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Hadzidimitriou, Anastasia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Plevova, Karla
    Rossi, Davide
    Malcikova, Jitka
    Stalika, Evangelia
    Pedersen, Lone Bredo
    Agathangelidis, Andreas
    Davis, Zadie
    Mansouri, Larry
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Scarfo, Lydia
    Boudjogra, Myriam
    Navarro, Alba
    Muggen, Alice
    Yan, Xiao-Jie
    Panagiotidis, Panagiotis
    Chiorazzi, Nicholas
    Geisler, Christian
    Belessi, Chrysoula
    Campo, Elias
    Stretford, Jonathan C.
    Ghia, Paolo
    Langerak, Anton W.
    Oscier, David
    Gaidano, Gianluca
    Pospisilova, Sarka
    Davi, Frederic
    Stamatopoulos, Kostas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Rosenquist, Richard Brandell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Subset-Specific Spectra of Recurrent Gene Mutations in Chronic Lymphocytic Leukemia with Stereotyped B-Cell Receptors2014In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 124, no 21Article in journal (Other academic)
  • 40. Xochelli, A.
    et al.
    Agathangelidis, A.
    Kavakiotis, I.
    Minga, E.
    Sutton, L. A.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Baliakas, Panagiotis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Hematology and Immunology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Chouvarda, I.
    Giudicelli, V.
    Vlahavas, I.
    Maglaveras, N.
    Bonello, L.
    Trentin, L.
    Montillo, M.
    Panagiotidis, P.
    Geisler, C.
    Langerak, A. W.
    Pospisilova, S.
    Jelinek, D. F.
    Oscier, D.
    Chiorazzi, N.
    Darzentas, N.
    Davi, F.
    Ghia, P.
    Rosenquist, Richard Brandell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Hematology and Immunology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Hadzidimitriou, A.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Belessi, C.
    Lefranc, M. P.
    Stamatopoulos, K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Immunoglobulin Heavy Variable Genes and Alleles: New Entities, New Names and Implications for Research and Prognostication in CLL2014In: Haematologica (online), ISSN 0390-6078, E-ISSN 1592-8721, Vol. 99, no S1, p. 49-49Article in journal (Other academic)
  • 41. Xochelli, Aliki
    et al.
    Agathangelidis, Andreas
    Kavakiotis, Ioannis
    Minga, Evangelia
    Sutton, Lesley Ann
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Baliakas, Panagiotis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Chouvarda, Ioanna
    Giudicelli, Veronique
    Vlahavas, Ioannis
    Maglaveras, Nikos
    Bonello, Lisa
    Trentin, Livio
    Tedeschi, Alessandra
    Panagiotidis, Panagiotis
    Geisler, Christian
    Langerak, Anton W.
    Pospisilova, Sarka
    Jelinek, Diane F.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Oscier, David
    Chiorazzi, Nicholas
    Darzentas, Nikos
    Davi, Fred
    Ghia, Paolo
    Rosenquist, Richard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Hadzidimitriou, Anastasia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Belessi, Chrysoula
    Lefranc, Marie-Paule
    Stamatopoulos, Kostas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Immunoglobulin heavy variable (IGHV) genes and alleles: new entities, new names and implications for research and prognostication in chronic lymphocytic leukaemia2015In: Immunogenetics, ISSN 0093-7711, E-ISSN 1432-1211, Vol. 67, no 1, p. 61-66Article in journal (Refereed)
    Abstract [en]

    Ieext generation sequencing studies in Homo sapiens have identified novel immunoglobulin heavy variable (IGHV) genes and alleles necessitating changes in the international ImMunoGeneTics information system (IMGT) GENE-DB and reference directories of IMGT/V-QUEST. In chronic lymphocytic leukaemia (CLL), the somatic hypermutation (SHM) status of the clonotypic rearranged IGHV gene is strongly associated with patient outcome. Correct determination of this parameter strictly depends on the comparison of the nucleotide sequence of the clonotypic rearranged IGHV gene with that of the closest germline counterpart. Consequently, changes in the reference directories could, in principle, affect the correct interpretation of the IGHV mutational status in CLL. To this end, we analyzed 8066 productive IG heavy chain (IGH) rearrangement sequences from our consortium both before and after the latest update of the IMGT/V-QUEST reference directory. Differences were identified in 405 cases (5 % of the cohort). In 291/405 sequences (71.9 %), changes concerned only the IGHV gene or allele name, whereas a change in the percent germline identity (%GI) was noted in 114/405 (28.1 %) sequences; in 50/114 (43.8 %) sequences, changes in the %GI led to a change in the mutational set. In conclusion, recent changes in the IMGT reference directories affected the interpretation of SHM in a sizeable number of IGH rearrangement sequences from CLL patients. This indicates that both physicians and researchers should consider a re-evaluation of IG sequence data, especially for those IGH rearrangement sequences that, up to date, have a GI close to 98 %, where caution is warranted.

  • 42.
    Xochelli, Aliki
    et al.
    CERTH, Inst Appl Biosci, Thessaloniki, Greece.;Ctr Res & Technol Hellas, Thessaloniki, Greece..
    Baliakas, Panagiotis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Agathangelidis, Andreas
    Hadzidimitriou, Anastasia
    CERTH, Inst Appl Biosci, Thessaloniki, Greece.;IRCCS San Raffaele Sci Inst, Div Expt Oncol, Milan, Italy.;IRCCS San Raffaele Sci Inst, Dept Oncohematol, Milan, Italy..
    Sutton, Lesley-Ann
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Minga, Eva
    CERTH, Inst Appl Biosci, Thessaloniki, Greece..
    Tausch, Eugen
    Univ Ulm, Dept Internal Med 3, Med Ctr, D-89069 Ulm, Germany..
    Yan, Xiao J.
    North Shore LIJ Hlth Syst, Feinstein Inst Med Res, Manhasset, NY USA..
    Shanafelt, Tait D.
    Mayo Clin, Dept Hematol, Rochester, MN USA..
    Plevova, Karla
    Masaryk Univ, Dept Internal Med Hematol & Oncol, Univ Hosp Brno, Brno, Czech Republic.;Masaryk Univ, Fac Med, Brno, Czech Republic..
    Boudjogra, Myriam
    Hop La Pitie Salpetriere, Dept Hematol, Paris, France.;Univ Paris 06, Paris, France..
    Rossi, Davide
    Amedeo Avogadro Univ Eastern Piedmont, Dept Translat Med, Div Hematol, Novara, Italy..
    Davis, Zadie
    Royal Bournemouth Hosp, Dept Haematol, Bournemouth, Dorset, England..
    Navarro, Alba
    Univ Barcelona, Hosp Clin, Inst Invest Biomed August Pi & Sunyer IDIBAPS, Barcelona, Spain..
    Sandberg, Yorick
    Univ Med Ctr Rotterdam, Erasmus MC, Dept Immunol, Rotterdam, Netherlands..
    Vojdeman, Fie Juhl
    Rigshosp, Dept Hematol, DK-2100 Copenhagen, Denmark..
    Scarfo, Lydia
    IRCCS San Raffaele Sci Inst, Div Expt Oncol, Milan, Italy..
    Stavroyianni, Niki
    G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    Sudarikov, Andrey B.
    Natl Res Ctr Hematol, Moscow, Russia..
    Veronese, Silvio
    Osped Niguarda Ca Granda, Niguarda Canc Ctr, Mol Pathol Unit, Milan, Italy.;Osped Niguarda Ca Granda, Niguarda Canc Ctr, Dept Haematol, Milan, Italy..
    Tzenou, Tatiana
    Univ Athens, Laikon Univ Hosp, Sch Med, Hematol Sect,Dept Propaedeut Med 1, Athens 11528, Greece..
    Karan-Djurasevic, Teodora
    Univ Belgrade, Inst Mol Genet & Genet Engn, Belgrade, Serbia..
    Catherwood, Mark
    Belfast City Hosp, Dept Haematooncol, Belfast BT9 7AD, Antrim, North Ireland..
    Kienle, Dirk
    Univ Ulm, Dept Internal Med 3, D-89069 Ulm, Germany..
    Chatzouli, Maria
    Nikea Gen Hosp, Dept Hematol, Piraeus, Greece..
    Facco, Monica
    Univ Padua, Dept Med, Hematol & Clin Immunol Sect, Sch Med, Padua, Italy..
    Bahlo, Jasmin
    Univ Hosp, Dept Internal Med 1, Ctr Integrated Oncol Cologne Bonn, Cologne, Germany..
    Pedersen, Lone Bredo
    Rigshosp, Dept Hematol, DK-2100 Copenhagen, Denmark..
    Mansouri, Larry
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Smedby, Karin E.
    Karolinska Inst, Dept Med, Clin Epidemiol Unit, Stockholm, Sweden..
    Chu, Charles C.
    North Shore LIJ Hlth Syst, Feinstein Inst Med Res, Manhasset, NY USA..
    Giudicelli, Veronique
    Univ Montpellier, LIGM, IGH, IMGT Int ImMunoGeneT informat Syst,UPR CNRS 1142, F-34059 Montpellier, France..
    Lefranc, Marie-Paule
    Univ Montpellier, LIGM, IGH, IMGT Int ImMunoGeneT informat Syst,UPR CNRS 1142, F-34059 Montpellier, France..
    Panagiotidis, Panagiotis
    Univ Athens, Dept Propaedeut Med 1, Athens, Greece..
    Juliusson, Gunnar
    Lund Univ, Lund, Sweden.;Lund Stem Cell Ctr, Hosp Dept Hematol, Lund, Sweden..
    Anagnostopoulos, Achilles
    G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    Antic, Darko
    Univ Belgrade, Ctr Clin, Clin Hematol, YU-11000 Belgrade, Serbia.;Univ Belgrade, Fac Med, Belgrade, Serbia..
    Trentin, Livio
    Univ Sch Med, Hematol & Clin Immunol Branch, Dept Med, Padua, Italy..
    Montillo, Marco
    Osped Niguarda Ca Granda, Niguarda Canc Ctr, Mol Pathol Unit, Milan, Italy..
    Niemann, Carsten
    Rigshosp, Dept Hematol, DK-2100 Copenhagen, Denmark..
    Dohner, Hartmut
    Univ Hosp, Dept Internal Med 3, Ulm, Germany..
    Langerak, Anton W.
    Erasmus MC, Dept Immunol, Rotterdam, Netherlands..
    Darzentas, Nikos
    Masaryk Univ, Cent European Inst Technol, Brno, Czech Republic..
    Pospisilova, Sarka
    Masaryk Univ, Cent European Inst Technol, Brno, Czech Republic..
    Hallek, Michael
    Univ Hosp, Dept Internal Med, Cologne, Germany.;Univ Hosp, Ctr Integrated Oncol, Cologne, Germany..
    Campo, Elias
    Univ Barcelona, Hosp Clin, Inst Invest Biomed August Pi & Sunyer IDIBAPS, Barcelona, Spain.;Univ Med Ctr Rotterdam, Erasmus MC, Dept Immunol, Rotterdam, Netherlands..
    Chiorazzi, Nicholas
    North Shore LIJ Hlth Syst, Feinstein Inst Med Res, Manhasset, NY USA..
    Oscier, David
    Royal Bournemouth Hosp, Dept Haematol, Bournemouth, Dorset, England..
    Gaidano, Gianluca
    Amedeo Avogadro Univ Eastern Piedmont, Dept Translat Med, Div Haematol, Novara, Italy..
    Belessi, Chrysoula
    Nikea Gen Hosp, Dept Hematol, Piraeus, Greece..
    Jelinek, Diane F.
    Mayo Clin, Dept Immunol, Rochester, MN USA..
    Stilgenbauer, Stephan
    Univ Ulm, Dept Internal Med 3, D-89069 Ulm, Germany..
    Davi, Frederic
    Hop La Pitie Salpetriere, Dept Hematol, Paris, France..
    Rosenquist, Richard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Ghia, Paolo
    IRCCS San Raffaele Sci Inst, Div Expt Oncol, Milan, Italy..
    Stamatopoulos, Kostas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. CERTH, Inst Appl Biosci, Thessaloniki, Greece.;G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    CLL with Mutated IGHV4-34 Antigen Receptors Is Clinically Heterogeneous: Antigen Receptor Stereotypy Makes the Difference2015In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 126, no 23Article in journal (Other academic)
  • 43.
    Xochelli, Aliki
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab. CERTH, Inst Appl Biosci, Thessaloniki, Greece.
    Baliakas, Panagiotis
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. ..
    Kavakiotis, Ioannis
    Aristotle Univ Thessaloniki, Dept Informat, Thessaloniki, Greece..
    Agathangelidis, Andreas
    CERTH, Inst Appl Biosci, Thessaloniki, Greece.;IRCCS San Raffaele Sci Inst, Div Expt Oncol, Milan, Italy.;IRCCS San Raffaele Sci Inst, Dept Oncohematol, Milan, Italy..
    Sutton, Lesley Ann
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab. Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden..
    Minga, Eva
    CERTH, Inst Appl Biosci, Thessaloniki, Greece..
    Ntoufa, Stavroula
    CERTH, Inst Appl Biosci, Thessaloniki, Greece..
    Tausch, Eugen
    Ulm Univ, Dept Internal Med 3, Ulm, Germany..
    Yan, Xiao-Jie
    Northwell Hlth, Feinstein Inst Med Res, Manhasset, NY USA..
    Shanafelt, Tait
    Mayo Clin, Dept Med, Dept Hematol, Rochester, MN USA..
    Plevova, Karla
    Masaryk Univ, Cent European Inst Technol, Brno, Czech Republic..
    Boudjogra, Myriam
    Hop La Pitie Salpetriere, Dept Hematol, Paris, France.;Univ Paris 06, Paris, France..
    Rossi, Davide
    Univ Piemonte Orientale, Dept Translat Med, Dept Haematol, Novara, Italy..
    Davis, Zadie
    Royal Bournemouth Hosp, Dept Haematol, Bournemouth, Dorset, England..
    Navarro, Alba
    Univ Barcelona, Inst Invest Biomed August Pi & Sunyer IDIBAPS, Hosp Clin, Barcelona, Spain..
    Sandberg, Yorick
    Univ Med Ctr Rotterdam, Erasmus MC, Dept Immunol, Rotterdam, Netherlands..
    Vojdeman, Fie Juhl
    Rigshosp, Dept Haematol, Copenhagen, Denmark..
    Scarfo, Lydia
    IRCCS San Raffaele Sci Inst, Div Expt Oncol, Milan, Italy.;IRCCS San Raffaele Sci Inst, Dept Oncohematol, Milan, Italy..
    Stavroyianni, Niki
    G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    Sudarikov, Andrey
    Natl Res Ctr Hematol, Moscow, Russia..
    Veronese, Silvio
    Osped Niguarda Ca Granda, Mol Pathol Unit, Milan, Italy.;Osped Niguarda Ca Granda, Dept Haematol, Milan, Italy..
    Tzenou, Tatiana
    Univ Athens, Dept Propaedeut Med 1, Athens, Greece..
    Karan-Djurasevic, Teodora
    Univ Belgrade, Inst Mol Genet & Genet Engn, Belgrade, Serbia..
    Catherwood, Mark
    Belfast City Hosp, Dept Haematooncol, Belfast, Antrim, North Ireland..
    Kienle, Dirk
    Ulm Univ, Dept Internal Med 3, Ulm, Germany..
    Chatzouli, Maria
    Nikea Gen Hosp, Dept Hematol, Piraeus, Greece..
    Facco, Monica
    Univ Padua, Sch Med, Hematol & Clin Immunol Branch, Dept Med, Padua, Italy..
    Bahlo, Jasmin
    Univ Hosp Cologne, Dept Internal Med 1, Cologne, Germany.;Univ Hosp Cologne, Ctr Integrated Oncol, Cologne, Germany..
    Pott, Christiane
    Univ Hosp Schleswig Holstein, Med Dept 2, Campus Kiel, Kiel, Germany..
    Pedersen, Lone Bredo
    Rigshosp, Dept Haematol, Copenhagen, Denmark..
    Mansouri, Larry
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden..
    Smedby, Karin E.
    Karolinska Inst, Clin Epidemiol Unit, Dept Med Solna, Stockholm, Sweden..
    Chu, Charles C.
    Northwell Hlth, Feinstein Inst Med Res, Manhasset, NY USA..
    Giudicelli, Veronique
    Univ Montpellier, CNRS, UPR 1142, IMGT,LIGM,IGH, Montpellier, France..
    Lefranc, Marie-Paule
    Univ Montpellier, CNRS, UPR 1142, IMGT,LIGM,IGH, Montpellier, France..
    Panagiotidis, Panagiotis
    Univ Athens, Dept Propaedeut Med 1, Athens, Greece..
    Juliusson, Gunnar
    Lund Univ, Lund, Sweden.;Lund Stem Cell Ctr, Hosp Dept Hematol, Lund, Sweden..
    Anagnostopoulos, Achilles
    G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    Vlahavas, Ioannis
    Aristotle Univ Thessaloniki, Dept Informat, Thessaloniki, Greece..
    Antic, Darko
    Ctr Clin, Clin Hematol, Belgrade, Serbia.;Univ Belgrade, Fac Med, Belgrade, Serbia..
    Trentin, Livio
    Univ Padua, Sch Med, Hematol & Clin Immunol Branch, Dept Med, Padua, Italy..
    Montillo, Marco
    Osped Niguarda Ca Granda, Mol Pathol Unit, Milan, Italy.;Osped Niguarda Ca Granda, Dept Haematol, Milan, Italy..
    Niemann, Carsten
    Rigshosp, Dept Haematol, Copenhagen, Denmark..
    Doehner, Hartmut
    Ulm Univ, Dept Internal Med 3, Ulm, Germany..
    Langerak, Anton W.
    Univ Med Ctr Rotterdam, Erasmus MC, Dept Immunol, Rotterdam, Netherlands..
    Pospisilova, Sarka
    Masaryk Univ, Cent European Inst Technol, Brno, Czech Republic..
    Hallek, Michael
    Univ Hosp Cologne, Dept Internal Med 1, Cologne, Germany.;Univ Hosp Cologne, Ctr Integrated Oncol, Cologne, Germany..
    Campo, Elias
    Univ Barcelona, Inst Invest Biomed August Pi & Sunyer IDIBAPS, Hosp Clin, Barcelona, Spain..
    Chiorazzi, Nicholas
    Northwell Hlth, Feinstein Inst Med Res, Manhasset, NY USA..
    Maglaveras, Nikos
    Aristotle Univ Thessaloniki, Lab Med Informat, Thessaloniki, Greece..
    Oscier, David
    Royal Bournemouth Hosp, Dept Haematol, Bournemouth, Dorset, England..
    Gaidano, Gianluca
    Univ Piemonte Orientale, Dept Translat Med, Dept Haematol, Novara, Italy..
    Jelinek, Diane F.
    Mayo Clin, Dept Immunol, Rochester, MN USA..
    Stilgenbauer, Stephan
    Ulm Univ, Dept Internal Med 3, Ulm, Germany..
    Chouvarda, Ioanna
    Aristotle Univ Thessaloniki, Lab Med Informat, Thessaloniki, Greece..
    Darzentas, Nikos
    Masaryk Univ, Cent European Inst Technol, Brno, Czech Republic..
    Belessi, Chrysoula
    Nikea Gen Hosp, Dept Hematol, Piraeus, Greece..
    Davi, Frederic
    Hop La Pitie Salpetriere, Dept Hematol, Paris, France.;Univ Paris 06, Paris, France..
    Hadzidimitriou, Anastasia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab. CERTH, Inst Appl Biosci, Thessaloniki, Greece..
    Rosenquist, Richard
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden..
    Ghia, Paolo
    IRCCS San Raffaele Sci Inst, Div Expt Oncol, Milan, Italy.;IRCCS San Raffaele Sci Inst, Dept Oncohematol, Milan, Italy.;Univ Vita Salute San Raffaele, Milan, Italy.;IRCCS Ist Sci San Raffaele, Milan, Italy..
    Stamatopoulos, Kostas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. CERTH, Inst Appl Biosci, Thessaloniki, Greece ;G Papanicolaou Hosp, Dept Hematol, Thessaloniki, Greece.;G Papanicolaou Hosp, HCT Unit, Thessaloniki, Greece..
    Chronic Lymphocytic Leukemia with Mutated IGHV4-34 Receptors: Shared and Distinct Immunogenetic Features and Clinical Outcomes2017In: Clinical Cancer Research, ISSN 1078-0432, E-ISSN 1557-3265, Vol. 23, no 17, p. 5292-5301Article in journal (Refereed)
    Abstract [en]

    Purpose: We sought to investigate whether B cell receptor immunoglobulin (BcR IG) stereotypy is associated with particular clinicobiological features among chronic lymphocytic leukemia (CLL) patients expressing mutated BcR IG (M-CLL) encoded by the IGHV4-34 gene, and also ascertain whether these associations could refine prognostication. Experimental Design: In a series of 19,907 CLL cases with available immunogenetic information, we identified 339 IGHV4-34expressing cases assigned to one of the four largest stereotyped M-CLL subsets, namely subsets #4, #16, #29 and #201, and investigated in detail their clinicobiological characteristics and disease outcomes. Results: We identified shared and subset-specific patterns of somatic hypermutation (SHM) among patients assigned to these subsets. The greatest similarity was observed between subsets #4 and #16, both including IgG-switched cases (IgG-CLL). In contrast, the least similarity was detected between subsets #16 and #201, the latter concerning IgM/D-expressing CLL. Significant differences between subsets also involved disease stage at diagnosis and the presence of specific genomic aberrations. IgG subsets #4 and #16 emerged as particularly indolent with a significantly (P < 0.05) longer time-to-first-treatment (TTFT; median TTFT: not yet reached) compared with the IgM/D subsets #29 and #201 (median TTFT: 11 and 12 years, respectively). Conclusions: Our findings support the notion that BcR IG stereotypy further refines prognostication in CLL, superseding the immunogenetic distinction based solely on SHM load. In addition, the observed distinct genetic aberration landscapes and clinical heterogeneity suggest that not all M-CLL cases are equal, prompting further research into the underlying biological background with the ultimate aim of tailored patient management.  

  • 44. Xochelli, Aliki
    et al.
    Baliakas, Panagiotis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Hematology and Immunology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Moore, Sarah
    Sole, Francesc
    Wickham, Nicholas
    Salido, Marta
    Athanasiadou, Anastasia
    Oscier, David
    Stamatopoulos, Kostas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Trans location t(2;7)(p11.2;q21.2): a rare genetic aberration associated with B-cell lymphoproliferative disorders of marginal-zone origin2014In: Cancer Genetics and Cytogenetics, ISSN 2210-7762, E-ISSN 2210-7770, Vol. 207, no 6, p. 281-283Article in journal (Refereed)
  • 45. Xochelli, Aliki
    et al.
    Kalpadakis, Christina
    Gardiner, Anne
    Baliakas, Panagiotis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Hematology and Immunology.
    Vassilakopoulos, Theodoros P.
    Mould, Sarah
    Davis, Zadie
    Stalika, Evangelia
    Kanellis, George
    Angelopoulou, Maria K.
    McIver-Brown, Neil
    Ibbotson, Rachel
    Sachanas, Sotirios
    Korkolopoulou, Penelope
    Athanasiadou, Anastasia
    Anagnostopoulos, Achilles
    Papadaki, Helen A.
    Papadaki, Theodora
    Stamatopoulos, Kostas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Pangalis, Gerassimos A.
    Oscier, David
    Clonal B-cell lymphocytosis exhibiting immunophenotypic features consistent with a marginal-zone origin: is this a distinct entity?2014In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 123, no 8, p. 1199-1206Article in journal (Refereed)
    Abstract [en]

    The biological and clinical significance of a clonal B-cell lymphocytosis with an immunophenotype consistent with marginal-zone origin (CBL-MZ) is poorly understood. We retrospectively evaluated 102 such cases with no clinical evidence to suggest a concurrent MZ lymphoma. Immunophenotyping revealed a clonal B-cell population with Matutes score <= 2 in all cases; 19/102 were weakly CD5 positive and all 35 cases tested expressed CD49d. Bone marrow biopsy exhibited mostly mixed patterns of small B-lymphocytic infiltration. A total of 48/66 (72.7%) cases had an abnormal karyotype. Immunogenetics revealed overusage of the IGHV4-34 gene and somatic hypermutation in 71/79 (89.8%) IGHV-IGHD-IGHJ gene rearrangements. With a median follow-up of 5 years, 85 cases remain stable (group A), whereas 17 cases (group B) progressed, of whom 15 developed splenomegaly. The clonal B-cell count, degree of marrow infiltration, immunophenotypic, or immunogenetic findings at diagnosis did not distinguish between the 2 groups. However, deletions of chromosome 7q were confined to group A and complex karyotypes were more frequent in group B. Although CBL-MZ may antedate SMZL/SLLU, most cases remain stable over time. These cases, not readily classifiable within the World Heath Organization classification, raise the possibility that CBL-MZ should be considered as a new provisional entity within the spectrum of clonal MZ disorders.

  • 46.
    Young, Emma
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Noerenberg, Daniel
    Department of Hematology, Oncology, and Tumor Immunology, Charité, University Medical Center, Berlin, Germany.
    Mansouri, Larry
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Ljungström, Viktor
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Frick, Mareike
    Department of Hematology, Oncology, and Tumor Immunology, Charité, University Medical Center, Berlin, Germany.
    Sutton, Lesley Ann
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Blakemore, Stuart James
    Cancer Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.
    Galan-Sousa, Joel
    Department of Hematology, Oncology, and Tumor Immunology, Charité, University Medical Center, Berlin, Germany.
    Plevova, Karla
    Central European Institute of Technology, Masaryk University and University Hospital Brno, Brno, Czech Republic.
    Baliakas, Panagiotis
    Uppsala University, Science for Life Laboratory, SciLifeLab.
    Rossi, Davide
    Division of Hematology, Department of Translational Medicine, Amedeo Avogadro University of Eastern Piedmont, Novara, Italy and Hematology, Oncology Institute of Southern Switzerland and Institute of Oncology Research, Bellinzona, Switzerland.
    Ruth, Clifford
    Oxford National Institute for Health Research Biomedical Research Centre and Department of Oncology, University of Oxford, Oxford, UK.
    Roos-Weil, Damien
    INSERM, U1170, Institut Gustave Roussy, Villejuif, France.
    Navrklova, Veronika
    European Institute of Technology, Masaryk University and University Hospital Brno, Brno, Czech Republic.
    Dörken, Bernd
    Department of Hematology, Oncology, and Tumor Immunology, Charité, University Medical Center, Berlin, Germany.
    Schmitt, Clemens A
    Department of Hematology, Oncology, and Tumor Immunology, Charité, University Medical Center, Berlin, Germany.
    Ekström Smedby, Karin
    Department of Medicine Solna, Clinical Epidemiology Unit, Karolinska Institutet, and Hematology Center, Karolinska University Hospital, Stockholm, Sweden.
    Juliusson, Gunnar
    Department of Laboratory Medicine, Stem Cell Center, Lund University, Lund, Sweden.
    Giacopelli, Brian
    Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH, USA.
    Blachly, James
    Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH, USA.
    Belessi, Chrysoula
    Hematology Department, General Hospital of Nikea, Piraeus, Greece.
    Panayiotidis, Panayiotis
    First Department of Propaedeutic Medicine, School of Medicine, University of Athens, Athens, Greece.
    Chiorazzi, Nicholas
    Karches Center for Chronic Lymphocytic Leukemia Research, The Feinstein Institute for Medical Research, Manhasset, New York, USA.
    Davi, Frédéric
    Laboratory of Hematology and Universite Pierre et Marie Curie, Hopital Pitie-Salpetriere, Paris, France.
    Langerak, Anton W
    Department of Immunology, Laboratory for Medical Immunology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
    Oscier, David
    Department of Molecular Pathology, Royal Bournemouth Hospital, Bournemouth, UK.
    Schuh, Anna
    Oxford National Institute for Health Research Biomedical Research Centre and Department of Oncology, University of Oxford, Oxford, UK.
    Gaidano, Gianluca
    Division of Hematology, Department of Translational Medicine, Amedeo Avogadro University of Eastern Piedmont, Novara, Italy.
    Ghia, Paolo
    Università Vita-Salute San Raffaele, Milan, Italy and Division of Experimental Oncology and Department of Onco-Hematology, Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele Scientific Institute, Milan, Italy.
    Xu, Wei
    Department of Hematology, the First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Collaborative Innovation Center For Cancer Personalized Medicine, Nanjing, China.
    Fan, Lei
    Department of Hematology, the First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Collaborative Innovation Center For Cancer Personalized Medicine, Nanjing, China.
    Bernard, Olivier A
    INSERM, U1170, Institut Gustave Roussy, Villejuif, France.
    Nguyen-Khac, Florence
    Laboratory of Hematology and Universite Pierre et Marie Curie, Hopital Pitie-Salpetriere, Paris, France.
    Rassenti, Laura Z
    Division of Hematology/Oncology, Department of Medicine, University of California at San Diego/Moores Cancer Center, La Jolla, CA, USA.
    Li, Jianyonglm
    Department of Hematology, the First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Collaborative Innovation Center For Cancer Personalized Medicine, Nanjing, China.
    Kipps, Thomas J
    Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH, USA.
    Stamatopoulos, Kostas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab. Department of Immunology, Genetics, and Pathology, Science for Life Laboratory, Uppsala University, Sweden and Institute of Applied Biosciences, Center for Research and Technology Hellas, Thessaloniki, Greece.
    Pospisilova, Sarka
    Central European Institute of Technology, Masaryk University and University Hospital Brno, Brno, Czech Republic.
    Zenz, Thorsten
    Department of Molecular Therapy in Haematology and Oncology (G250) and Department of Translational Oncology, National Center for Tumor Diseases (NCT), German Cancer Research Center (DKFZ), Heidelberg, Germany; Department of Medicine V, University Hospital Heidelberg, Heidelberg, Germany and German Consortium for Translational Cancer Research (DKTK), Heidelberg, Germany.
    Strefford, Jonathan
    Cancer Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.
    Rosenquist, Richard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Damm, Frederik
    Department of Hematology, Oncology, and Tumor Immunology, Charité, University Medical Center, Berlin, Germany; German Consortium for Translational Cancer Research (DKTK), Heidelberg, Germany and Berlin Institute of Health (BIH), Berlin, Germany .
    EGR2 mutations define a new clinically aggressive subgroup of chronic lymphocytic leukemia2017In: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 31, no 7, p. 1547-1554Article in journal (Refereed)
    Abstract [en]

    Recurrent mutations within EGR2 were recently reported in advanced-stage chronic lymphocytic leukemia (CLL) patients and associated with a worse outcome. To study their prognostic impact, 2403 CLL patients were examined for mutations in the EGR2 hotspot region including a screening (n = 1283) and two validation cohorts (UK CLL4 trial patients, n = 366; CLL Research Consortium (CRC) patients, n = 490). Targeted deep-sequencing of 27 known/postulated CLL driver genes was also performed in 38 EGR2-mutated patients to assess concurrent mutations. EGR2 mutations were detected in 91/2403 (3.8%) investigated cases, and associated with younger age at diagnosis, advanced clinical stage, high CD38 expression and unmutated IGHV genes. EGR2- mutated patients frequently carried ATM lesions (42%), TP53 aberrations (18%) and NOTCH1/FBXW7 mutations (16%). EGR2 mutations independently predicted shorter time-to-first-treatment (TTFT) and overall survival (OS) in the screening cohort; they were confirmed associated with reduced TTFT and OS in the CRC cohort and independently predicted short OS from randomization in the UK CLL4 cohort. A particularly dismal outcome was observed among EGR2-mutated patients who also carried TP53 aberrations. In summary, EGR2 mutations were independently associated with an unfavorable prognosis, comparable to CLL patients carrying TP53 aberrations, suggesting that EGR2-mutated patients represent a new patient subgroup with very poor outcome.

  • 47.
    Young, Emma
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Norenberg, Daniel
    Charite, Dept Hematol Oncol & Tumor Immunol, D-13353 Berlin, Germany..
    Ljungstrom, Viktor
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Mansouri, Larry
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Plevova, Karla
    Masaryk Univ, Cent European Inst Technol, Brno, Czech Republic..
    Baliakas, Panagiotis
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Rossi, Davide
    Amedeo Avogadro Univ Eastern Piedmont, Novara, Italy..
    Navrkalova, Veronika
    Masaryk Univ, Cent European Inst Technol, Brno, Czech Republic..
    Sutton, Lesley-Ann
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Smedby, Karin Ekstrom
    Karolinska Inst, Clin Epidemiol Unit, Dept Med, Stockholm, Sweden..
    Juliusson, Gunnar
    Lund Univ, Dept Lab Med, Stem Cell Ctr Hematol & Transplantat, Lund, Sweden..
    Belessi, Chrysoula
    Gen Hosp Nikea, Dept Hematol, Piraeus, Greece..
    Panagiotidis, Panagiotis
    Univ Athens, Sch Med, Dept Propaedeut Med 1, GR-11527 Athens, Greece..
    Chiorazzi, Nicholas
    Feinstein Inst Med Res, North Shore Long Isl Jewish Hlth Syst, Manhasset, NY USA..
    Davi, Frederic
    Hop La Pitie Salpetriere, Hematol Lab, Paris, France.;Univ Paris 06, 12 Rue Cuvier, Paris, France..
    Langerak, Anton W.
    Univ Med Ctr Rotterdam, Erasmus MC, Dept Immunol, Rotterdam, Netherlands..
    Gaidano, Gianluca
    Ghia, Paolo
    IRCCS, San Raffaele Sci Inst, Div Expt Oncol, Milan, Italy.;IRCCS, San Raffaele Sci Inst, Dept Oncohematol, Milan, Italy..
    Stamatopoulos, Kostas
    CERTH, Inst Appl Biosci, Thessaloniki, Greece..
    Pospisilova, Sarka
    Masaryk Univ, Cent European Inst Technol, Brno, Czech Republic..
    Zenz, Thorsten
    Univ Heidelberg Hosp, Dept Med 5, Heidelberg, Germany..
    Rosenquist, Richard
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Damm, Frederik
    Charite, Dept Hematol Oncol & Tumor Immunol, D-13353 Berlin, Germany..
    EGR2 mutations in chronic lymphocytic leukemiam - a new bad player?2015In: Leukemia and Lymphoma, ISSN 1042-8194, E-ISSN 1029-2403, Vol. 56, no S1, p. 83-85Article in journal (Other academic)
1 - 47 of 47
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