Multidrug resistance‐1 gene polymorphisms associated with treatment outcomes in de novo acute myeloid leukemia

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 st...

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Bibliographic Details
Published in:International journal of cancer 2006-05, Vol.118 (9), p.2195-2201
Main Authors: 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
Format: Article
Language:English
Subjects:
Acute Disease
acute myeloid leukemia
Adolescent
Adult
Aged
Antineoplastic agents
ATP-Binding Cassette, Sub-Family B, Member 1 - genetics
Biological and medical sciences
Chemotherapy
Disease-Free Survival
Female
Genotype
Haplotypes
Humans
Leukemia, Myeloid - drug therapy
Leukemia, Myeloid - genetics
Male
Medical sciences
Middle Aged
multidrug resistance‐1 gene
Multivariate Analysis
Pharmacology. Drug treatments
Polymorphism, Single Nucleotide
single nucleotide polymorphism
Treatment Outcome
Tumors
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Summary: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.
ISSN:0020-7136
1097-0215
DOI:10.1002/ijc.21666