Association of ABCB1 polymorphisms with survival and in vitro cytotoxicty in de novo acute myeloid leukemia with normal karyotype
2012 (English)In: The Pharmacogenomics Journal, ISSN 1470-269X, E-ISSN 1473-1150, Vol. 12, no 2, 111-118 p.Article in journal (Refereed) Published
Overexpression of the multi-drug transporter P-glycoprotein, encoded by the ABCB1 gene, is a clinically relevant problem in acute myeloid leukemia (AML). Polymorphisms in ABCB1 might contribute to cancer risk and therapeutic response. We therefore investigated the influence of polymorphisms G1199A, C1236T, G2677T/A and C3435T on cancer susceptibility, in vitro cytotoxicity and overall survival in 100 de novo AML patients with normal karyotype. Patients with 1236C/C or 2677G/G genotypes showed poorer survival than patients with other genotypes (P = 0.03 and P = 0.02, respectively). Both these genotypes were significant factors for survival in multivariate analysis, along with age, NPM1 and FLT3 mutation status. In vitro cytotoxicity studies demonstrated that leukemic cells from 1236T/T and 2677T/T patients were significantly more susceptible to mitoxantrone (P 0.02), and tended to be more susceptible to etoposide and daunorubicin (P = 0.07-0.09), but not to cytarabine. No significant difference in allele frequencies was found between patients and healthy volunteers (n = 400).
Place, publisher, year, edition, pages
Nature Publishing Group , 2012. Vol. 12, no 2, 111-118 p.
ABCB1, acute myeloid leukemia, single-nucleotide polymorphisms, anthracyclines
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-76805DOI: 10.1038/tpj.2010.79ISI: 000302133700004OAI: oai:DiVA.org:liu-76805DiVA: diva2:516847
Funding Agencies|Swedish Cancer Society||Swedish Research Council-Medicine||Cancer Society in Stockholm||Karolinska Institutet||County Council in Ostergotland||2012-04-202012-04-202014-01-15Bibliographically approved