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Multidrug resistance‐1 gene polymorphisms associated with treatment outcomes in de novo acute myeloid leukemia
Author(s) -
Kim Dong Hwan,
Park Jae Yong,
Sohn Sang Kyun,
Lee Nan Young,
Baek Jin Ho,
Jeon Seok Bong,
Kim Jong Gwang,
Suh Jang Soo,
Do Young Rok,
Lee Kyu Bo
Publication year - 2005
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.21666
Subject(s) - genotype , myeloid leukemia , single nucleotide polymorphism , haplotype , medicine , p glycoprotein , biology , leukemia , multiple drug resistance , gene , multivariate analysis , genetics , gastroenterology , oncology , immunology , microbiology and biotechnology , drug resistance
Multidrug resistance‐1 (MDR‐1) gene single nucleotide polymorphisms (SNPs) have been identified as associated with the treatment outcomes of acute myeloid leukemia (AML) in Caucasians; yet, similar evidence is lacking for Asian populations. A total of 101 AML patients were enrolled in the current study. Two MDR1 SNPs (C3435T and G2677T/A) were analyzed with PCR/RFLP assay. As regards C3435T polymorphism, C/C genotype was significantly correlated with lower functional P‐glycoprotein (P‐gp) activity in leukemic blasts (7.5%) compared with C/T (10.7%) or T/T genotype (19.9%, p = 0.029). In genotypic analyses, C/C at −3435 ( p = 0.05) and G/G at −2677 ( p = 0.04) were strongly associated with a higher probability of complete remission (CR). In addition, the 3‐year event‐free survival (EFS) was higher in G/G genotype at −2677 (60.6%) than nonG/G (21.9%; p = 0.0241), in C/C at −3435 was higher than nonC/C genotype ( p = 0.0139), and was higher in GC haplotype homozygote (58.2%) than nonGC homozygote (22.6%; p = 0.0427). In a multivariate analysis, the group without GC haplotype showed worse EFS ( p = 0.030), with unfavorable cytogenetic risk ( p = 0.008). However, no differences were noted in overall survival according to the MDR1 SNPs ( p = 0.491 for C3435T and p = 0.955 for G2677T/A). © 2005 Wiley‐Liss, Inc.