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Impact of ABCB 1 single nucleotide polymorphisms 1236C>T and 2677G>T on overall survival in FLT 3 wild‐type de novo AML patients with normal karyotype
Author(s) -
Jakobsen Falk Ingrid,
Fyrberg Anna,
Paul Esbjörn,
Nahi Hareth,
Hermanson Monica,
Rosenquist Richard,
Höglund Martin,
Palmqvist Lars,
Stockelberg Dick,
Wei Yuan,
Gréen Henrik,
Lotfi Kourosh
Publication year - 2014
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.13097
Subject(s) - single nucleotide polymorphism , snp , allele , medicine , wild type , gastroenterology , biology , immunology , genotype , genetics , gene , mutant
Summary 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 ( SNP s) of ABCB 1 , 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 FLT 3 and NPM 1 status, to further elucidate the influence of ABCB 1 SNP s. 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. FLT 3 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 FLT 3 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 ABCB 1 1236C>T and 2677G>T may be used as prognostic markers to distinguish relatively high risk patients in the intermediate risk FLT 3 wild‐type group, which may contribute to future individualizing of treatment strategies.