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Association of ABCB1 polymorphisms with prognostic outcomes of anthracycline and cytarabine in Chinese patients with acute myeloid leukemia

  • Pharmacogenetics
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Purpose

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.

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Acknowledgments

This work was supported by the National High-tech R&D Program of China 863 Program Grant (no. 2012AA02A517), Program for the Special Scientific Research Foundation of Doctor Disciplines in University of Ministry of Education of China Grant (no. 20110162110034), China Postdoctoral Science Foundation of China Grant (no. 2013M542145), Liaoning Province Finance Department Foundation of China Grant (no. 2008934), and Liaoning Province Dr. Start-up Foundation of China Grant (no. 20111111).

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    1. Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410008, People’s Republic of China

      Hui He, Jiye Yin, Xi Li, Yu Zhang, Xiaojing Xu, Juan Chen, Chenyue Qian, Honghao Zhou & Zhaoqian Liu

    2. Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Central South University, Changsha, 410078, People’s Republic of China

      Hui He, Jiye Yin, Xi Li, Yu Zhang, Xiaojing Xu, Juan Chen, Chenyue Qian, Honghao Zhou & Zhaoqian Liu

    3. Department of Hematology, Benxi Central Hospital of China Medical University, Benxi, 117000, People’s Republic of China

      Hui He

    4. Department of Hematology, The First Affiliated Hospital of China Medical University, Shenyang, 110001, People’s Republic of China

      Ming Zhai

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    He, H., Yin, J., Li, X. et al. Association of ABCB1 polymorphisms with prognostic outcomes of anthracycline and cytarabine in Chinese patients with acute myeloid leukemia. Eur J Clin Pharmacol 71, 293–302 (2015). https://doi.org/10.1007/s00228-014-1795-6

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