Multidrug resistance-1 gene polymorphisms associated with treatment outcomes in de novo acute myeloid leukemia
Article first published online: 5 DEC 2005
Copyright © 2005 Wiley-Liss, Inc.
International Journal of Cancer
Volume 118, Issue 9, pages 2195–2201, 1 May 2006
How to Cite
Kim, D. H., Park, J. Y., Sohn, S. K., Lee, N. Y., Baek, J. H., Jeon, S. B., Kim, J. G., Suh, J. S., Do, Y. R. and Lee, K. B. (2006), Multidrug resistance-1 gene polymorphisms associated with treatment outcomes in de novo acute myeloid leukemia. Int. J. Cancer, 118: 2195–2201. doi: 10.1002/ijc.21666
- Issue published online: 21 FEB 2006
- Article first published online: 5 DEC 2005
- Manuscript Accepted: 4 OCT 2005
- Manuscript Received: 29 APR 2005
- Regional Technology Innovation Program of the Ministry of Commerce, Industry and Energy (MOCIE), The Republic of Korea. Grant Number: RTI04-01-01
- single nucleotide polymorphism;
- multidrug resistance-1 gene;
- 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). © 2005 Wiley-Liss, Inc.