title: Multidrug resistance-1 gene polymorphisms associated with treatment outcomes in de novo acute myeloid leukemia.
abstract: 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).
authors.affiliation: Department of Hematology/Oncology, Kyungpook National University Hospital, Daegu, Korea.
authors.forename: Dong Hwan
authors.initials: DH
authors.lastname: Kim
authors.forename: Jae Yong
authors.initials: JY
authors.lastname: Park
authors.forename: Sang Kyun
authors.initials: SK
authors.lastname: Sohn
authors.forename: Nan Young
authors.initials: NY
authors.lastname: Lee
authors.forename: Jin Ho
authors.initials: JH
authors.lastname: Baek
authors.forename: Seok Bong
authors.initials: SB
authors.lastname: Jeon
authors.forename: Jong Gwang
authors.initials: JG
authors.lastname: Kim
authors.forename: Jang Soo
authors.initials: JS
authors.lastname: Suh
authors.forename: Young Rok
authors.initials: YR
authors.lastname: Do
authors.forename: Kyu Bo
authors.initials: KB
authors.lastname: Lee
mesh_terms: 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
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1