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Association of ABCB1 polymorphisms with survival and in vitro cytotoxicty in de novo acute myeloid leukemia with normal karyotype
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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
Abstract [en]

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
2012. Vol. 12, no 2, 111-118 p.
Keyword [en]
ABCB1, acute myeloid leukemia, single-nucleotide polymorphisms, anthracyclines
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-173335DOI: 10.1038/tpj.2010.79ISI: 000302133700004OAI: oai:DiVA.org:uu-173335DiVA: diva2:517621
Available from: 2012-04-24 Created: 2012-04-23 Last updated: 2017-12-07Bibliographically approved

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Rosenquist, Richard

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