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Impact of ABCB1 single nucleotide polymorphisms 1236C>T and 2677G>T on overall survival in FLT3 wild-type de novo AML patients with normal karyotype
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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 1199G>A, 1236C>T, 2677G>T/A and 3435C>T, 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 1236C>T and 2677G>T 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
2014. Vol. 167, no 5, 671-680 p.
Keyword [en]
acute myeloid leukaemia, ABCB1, single nucleotide polymorphism, anthracyclines, FLT3
National Category
Biological Sciences
Identifiers
URN: urn:nbn:se:kth:diva-158806DOI: 10.1111/bjh.13097ISI: 000345222100009OAI: oai:DiVA.org:kth-158806DiVA: diva2:785186
Funder
Swedish Cancer SocietySwedish Research Council
Note

QC 20150202

Available from: 2015-02-02 Created: 2015-01-12 Last updated: 2017-12-05Bibliographically approved

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