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Impact of ABCB1 single nucleotide polymorphisms 1236C greater than T and 2677G greater than T on overall survival in FLT3 wild-type de novo AML patients with normal karyotype
Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences.ORCID iD: 0000-0003-4450-0333
Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences.
Karolinska Institute, Sweden.
Karolinska Institute, Sweden.
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2014 (English)In: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 167, no 5, 671-680 p.Article in journal (Refereed) Published
Abstract [en]

Drug resistance is a clinically relevant problem in the treatment of acute myeloid leukaemia (AML). We have previously reported a relationship between single nucleotide polymorphisms (SNPs) of ABCB1, encoding the multi-drug transporter P-glycoprotein, and overall survival (OS) in normal karyotype (NK)-AML. Here we extended this material, enabling subgroup analysis based on FLT3 and NPM1 status, to further elucidate the influence of ABCB1 SNPs. De novo NK-AML patients (n = 201) were analysed for 1199Ggreater thanA, 1236Cgreater thanT, 2677Ggreater thanT/A and 3435Cgreater thanT, and correlations to outcome were investigated. FLT3 wild-type 1236C/C patients have significantly shorter OS compared to patients carrying the variant allele; medians 20 vs. 49 months, respectively, P = 0.017. There was also an inferior outcome in FLT3 wild-type 2677G/G patients compared to patients carrying the variant allele, median OS 20 vs. 35 months, respectively, P = 0.039. This was confirmed in Cox regression analysis. Our results indicate that ABCB1 1236Cgreater thanT and 2677Ggreater thanT may be used as prognostic markers to distinguish relatively high risk patients in the intermediate risk FLT3 wild-type group, which may contribute to future individualizing of treatment strategies.

Place, publisher, year, edition, pages
Wiley , 2014. Vol. 167, no 5, 671-680 p.
Keyword [en]
acute myeloid leukaemia; ABCB1; single nucleotide polymorphism; anthracyclines; FLT3
National Category
Clinical Medicine
URN: urn:nbn:se:liu:diva-112996DOI: 10.1111/bjh.13097ISI: 000345222100009PubMedID: 25155901OAI: diva2:779143

Funding Agencies|Swedish Cancer Society; County Council of Ostergotland; AFA Insurance; Stockholm Cancer Society; Karolinska Institutet; Swedish Research Council

Available from: 2015-01-12 Created: 2015-01-08 Last updated: 2015-10-09

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Jakobsen Falk, IngridFyrberg, AnnaGreen, HenrikLotfi, Kourosh
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Division of Drug ResearchFaculty of Health SciencesDepartment of Clinical Pharmacology
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British Journal of Haematology
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