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

• 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
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.21666

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.