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Association between TERT promoter polymorphisms and acute myeloid leukemia risk and prognosis
Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Haematology.
Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.ORCID iD: 0000-0003-4450-0333
Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.
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2015 (English)In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 6, no 28, 25109-25120 p.Article in journal (Refereed) Published
Abstract [en]

Telomerase reverse transcriptase gene (TERT) promoter mutations are identified in many malignancies but not in hematological malignancies. Here we analyzed TERT and protection of telomeres 1 gene (POT1) mutations, and four different TERT SNVs in 226 acute myeloid leukemia (AML) patients and 806 healthy individuals in a case referent design, where also overall survival was assessed. A significant association for increased risk of AML was found for TERT SNVs, rs2853669 (OR = 2.45, p = 0.00015) and rs2736100 (OR = 1.5, p = 0.03). The overall survival for patients with CC genotype of rs2853669 was significantly shorter compared to those with TT or TC genotypes (p = 0.036 and 0.029 respectively). The influence of TERT rs2853669 CC on survival was confirmed in multivariable Cox regression analysis as an independent risk biomarker in addition to high risk group, higher age and treatment. No hot spot TERT promoter mutations at -228Cgreater thanT or -250Cgreater thanT or POT1 mutations could be identified in this AML cohort. We show that rs2853669 CC may be a risk factor for the development of AML that may also be used as a prognostic marker to identify high risk normal karyotype -AML (NK-AML) patients, for treatment guidance.

Place, publisher, year, edition, pages
Albany, NY, United States: Impact Journals LLC , 2015. Vol. 6, no 28, 25109-25120 p.
Keyword [en]
TERT; SNV; AML; prognostic markers
National Category
Clinical Medicine
Identifiers
URN: urn:nbn:se:liu:diva-122667DOI: 10.18632/oncotarget.4668ISI: 000363160100047OAI: oai:DiVA.org:liu-122667DiVA: diva2:871672
Note

Funding Agencies|Swedish Research Council; Swedish Cancer Society; County Council of Ostergotland; AFA Insurance; FORSS

Available from: 2015-11-16 Created: 2015-11-13 Last updated: 2017-12-01Bibliographically approved

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Mosrati, Mohamed AliWillander, KerstinJakobsen Falk, IngridLotfi, KouroshSöderkvist, Peter
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