Impact ofABCB1single nucleotide polymorphisms 1236C>T and 2677G>T on overall survival inFLT3wild‐typede novoAMLpatients with normal karyotype

• DOI: 10.1111/bjh.13097
• Publication Date: 2014-08-23T06:33:19Z
• 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
• Keywords: Adult; Male; 0301 basic medicine; ATP Binding Cassette Transporter, Subfamily B; Adolescent; Polymorphism, Single Nucleotide; Disease-Free Survival; 03 medical and health sciences; Risk Factors; Biomarkers, Tumor; Humans; Alleles; Aged; Aged, 80 and over; Klinisk medicin; Middle Aged; 3. Good health; Survival Rate; Leukemia, Myeloid, Acute; acute myeloid leukaemia; ABCB1; single nucleotide polymorphism; anthracyclines; FLT3; fms-Like Tyrosine Kinase 3; Female; Clinical Medicine; Nucleophosmin

SummaryDrug 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) ofABCB1, 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 onFLT3andNPM1status, to further elucidate the influence ofABCB1SNPs.De novoNK‐AMLpatients (n = 201) were analysed for 1199G>A, 1236C>T, 2677G>T/A and 3435C>T, and correlations to outcome were investigated.FLT3wild‐type 1236C/C patients have significantly shorterOScompared to patients carrying the variant allele; medians 20 vs. 49 months, respectively,P = 0·017. There was also an inferior outcome inFLT3wild‐type 2677G/G patients compared to patients carrying the variant allele, medianOS20 vs. 35 months, respectively,P = 0·039. This was confirmed in Cox regression analysis. Our results indicate thatABCB11236C>T and 2677G>T may be used as prognostic markers to distinguish relatively high risk patients in the intermediate riskFLT3wild‐type group, which may contribute to future individualizing of treatment strategies.