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

Authors

  • Dong Hwan Kim,

    1. Department of Hematology/Oncology, Kyungpook National University Hospital, Daegu, Korea
    2. Stem Cell Transplantation Center, Kyungpook National University Hospital, Daegu, Korea
    Search for more papers by this author
  • Jae Yong Park,

    Corresponding author
    1. Department of Pulmonary Medicine, Kyungpook National University Hospital, Daegu, Korea
    • Department of Hematology/Oncology or Department of Pulmonary Medicine, Kyungpook National University Hospital, 50 Samduk 2-ga, Jung-Gu, Daegu, Korea, 700-721
    Search for more papers by this author
    • Fax: 82-53-426-2046

  • Sang Kyun Sohn,

    Corresponding author
    1. Department of Hematology/Oncology, Kyungpook National University Hospital, Daegu, Korea
    2. Stem Cell Transplantation Center, Kyungpook National University Hospital, Daegu, Korea
    • Department of Hematology/Oncology or Department of Pulmonary Medicine, Kyungpook National University Hospital, 50 Samduk 2-ga, Jung-Gu, Daegu, Korea, 700-721
    Search for more papers by this author
  • Nan Young Lee,

    1. Department of Laboratory Medicine, Kyungpook National University Hospital, Daegu, Korea
    Search for more papers by this author
  • Jin Ho Baek,

    1. Department of Hematology/Oncology, Kyungpook National University Hospital, Daegu, Korea
    Search for more papers by this author
  • Seok Bong Jeon,

    1. Department of Hematology/Oncology, Kyungpook National University Hospital, Daegu, Korea
    Search for more papers by this author
  • Jong Gwang Kim,

    1. Department of Hematology/Oncology, Kyungpook National University Hospital, Daegu, Korea
    2. Stem Cell Transplantation Center, Kyungpook National University Hospital, Daegu, Korea
    Search for more papers by this author
  • Jang Soo Suh,

    1. Department of Laboratory Medicine, Kyungpook National University Hospital, Daegu, Korea
    Search for more papers by this author
  • Young Rok Do,

    1. Department of Hematology/Oncology, School of Medicine, Keimyung University, Daegu, Korea
    Search for more papers by this author
  • Kyu Bo Lee

    1. Department of Hematology/Oncology, Kyungpook National University Hospital, Daegu, Korea
    2. Stem Cell Transplantation Center, Kyungpook National University Hospital, Daegu, Korea
    Search for more papers by this author

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). © 2005 Wiley-Liss, Inc.

Ancillary