title: Association of ABCB1 polymorphisms with prognostic outcomes of anthracycline and cytarabine in Chinese patients with acute myeloid leukemia.
abstract: OBJECTIVE
  To investigate the influence of ABCB1 polymorphisms on prognostic outcomes in Chinese patients with de novo intermediate-risk acute myeloid leukemia (AML) and to examine the gene expression level in relation to the genetic variation.
  
  
  METHODS
  In total, 263 Chinese intermediate-risk AML patients treated with anthracycline and cytarabine were enrolled. G2677T, C1236T, and C3435T of the ABCB1 gene were analyzed by the allele-specific matrix-assisted laser desorption. Expression of ABCB1 messenger RNA (mRNA) was tested in 101 patients of known genotype and haplotype for ABCB1 polymorphisms. Basic clinical characteristics of these patients were collected from medical records.
  
  
  RESULTS
  Survival analysis showed that patients with AML (TTT haplotype) had a longer overall survival (OS) (p < 0.001, 29.2 months, 95 % confidence interval [CI], 26.9-31.5 months) and relapse-free survival (RFS) (p = 0.005, 21.8 months, 95 % CI, 19.5-24.0 months) compared with those without TTT haplotype (21.9 months, 95 % CI, 19.6-24.2 months; 16.5 months, 95 % CI, 14.6-18.5 months). After adjusting for age; gender; leukocyte count; hemoglobin level; platelet levels; French, American, and British classification; lactate dehydrogenase levels; Eastern Cooperative Oncology Group performance status; nucleophosmin gene; and fms-related tyrosine kinase 3 gene, the multivariate survival analysis showed that the TTT haplotype appeared to be a predicting factor for OS (p = 0.001, hazard ratio = 1.854, 95 % CI, 1.301-2.641) and RFS (p = 0.009, hazard ratio = 1.755, 95 % CI, 1.153-2.671). Moreover, a significant association between the TTT haplotype and relapse in AML patients was observed in this study (p = 0.002, odds ratio = 0.410, 95 % CI, 0.235-0.715). Gene expression level was significantly lower in patients with the TTT haplotype than in the patients with the other haplotypes (p = 0.004).
  
  
  CONCLUSIONS
  The findings suggested the TTT haplotype was possibly related to the OS, RFS, and relapse in Chinese patients with AML.
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410008, People's Republic of China.
authors.forename: Hui
authors.initials: H
authors.lastname: He
authors.forename: Jiye
authors.initials: J
authors.lastname: Yin
authors.forename: Xi
authors.initials: X
authors.lastname: Li
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Xu
authors.forename: Ming
authors.initials: M
authors.lastname: Zhai
authors.forename: Juan
authors.initials: J
authors.lastname: Chen
authors.forename: Chenyue
authors.initials: C
authors.lastname: Qian
authors.forename: Honghao
authors.initials: H
authors.lastname: Zhou
authors.forename: Zhaoqian
authors.initials: Z
authors.lastname: Liu
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000096:biosynthesis / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000368:Aged; D018943:Anthracyclines / Q000627:therapeutic use*; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D044466:Asian People / Q000235:genetics*; D003561:Cytarabine / Q000627:therapeutic use*; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012008:Recurrence; D016019:Survival Analysis; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D018943:Anthracyclines; D000964:Antimetabolites, Antineoplastic; D003561:Cytarabine