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 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).
Kim
Dong Hwan
DH
Department of Hematology/Oncology, Kyungpook National University Hospital, Daegu, Korea.
Park
Jae Yong
JY
Sohn
Sang Kyun
SK
Lee
Nan Young
NY
Baek
Jin Ho
JH
Jeon
Seok Bong
SB
Kim
Jong Gwang
JG
Suh
Jang Soo
JS
Do
Young Rok
YR
Lee
Kyu Bo
KB
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D018572:Disease-Free Survival; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D020641:Polymorphism, Single Nucleotide; D016896:Treatment Outcome
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1