Title |
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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Published in |
British Journal of Haematology, August 2014
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DOI | 10.1111/bjh.13097 |
Pubmed ID | |
Authors |
Ingrid Jakobsen Falk, Anna Fyrberg, Esbjörn Paul, Hareth Nahi, Monica Hermanson, Richard Rosenquist, Martin Höglund, Lars Palmqvist, Dick Stockelberg, Yuan Wei, Henrik Gréen, Kourosh Lotfi |
Abstract |
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. |
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Members of the public | 1 | 100% |
Mendeley readers
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United States | 1 | 5% |
Unknown | 18 | 95% |
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Student > Bachelor | 5 | 26% |
Researcher | 4 | 21% |
Student > Postgraduate | 3 | 16% |
Student > Ph. D. Student | 1 | 5% |
Other | 1 | 5% |
Other | 0 | 0% |
Unknown | 5 | 26% |
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Biochemistry, Genetics and Molecular Biology | 4 | 21% |
Pharmacology, Toxicology and Pharmaceutical Science | 1 | 5% |
Computer Science | 1 | 5% |
Agricultural and Biological Sciences | 1 | 5% |
Other | 0 | 0% |
Unknown | 5 | 26% |