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ABCB1 polymorphisms predict imatinib response in chronic myeloid leukemia patients: a systematic review and meta-analysis

The Pharmacogenomics Journal volume 15, pages 127–134 (2015)Cite this article

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Abstract

Imatinib mesylate, a competitive tyrosine kinase inhibitor, is considered the first-line therapy drug for Ph+ chronic myeloid leukemia (CML). Three single-nucleotide polymorphisms (SNPs) in the ATP-binding cassette, subfamily B (MDR/TAP), member 1 gene (ABCB1/MDR1), c.1236C>T, c.2677G>T/A and c.3435C>T, have been shown to affect cellular transport/metabolism of imatinib. The associations between these SNPs and imatinib response in CML patients have been widely evaluated, but the results were inconsistent. To derive a conclusive assessment of the associations, we performed a meta-analysis by combining data from a total of 12 reports including 1826 patients. The results showed that the 2677G allele or 3435T allele predicted a worse response to imatinib in CML patients, whereas 1236CC genotype was associated with better response in CML patients from Asian region. In conclusion, this meta-analysis suggests that c.1236C>T, c.2677G>T/A and c.3435C>T can be served as predictive markers for the therapeutical use of imatinib in CML patients.

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Acknowledgements

We would like to thank Dr Francisco Cervantes from Hematology Department, Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona, Spain for providing us their raw genotype data. Part of the work was supported by grant FAPESP, Brazil (#09/54184-0) to Dr Douglas Vivona.

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Authors and Affiliations

  1. Clinical Research Center, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China

    Q Zheng & J Cao

  2. Department of Neurosurgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China

    H Wu

  3. Department of Surgical Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China

    Q Yu

  4. Chronic Myelogenous Leukemia Group, Princess Margaret Cancer Centre, University Health Network University of Toronto, Toronto, Ontario, Canada

    D H (Dennis) Kim & J H Lipton

  5. Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy

    S Angelini

  6. Department of Experimental, Diagnostic and Specialty Medicine, Institute of Hematology, University of Bologna, Bologna, Italy

    S Soverini

  7. Departmento de Análises Clínicas e Toxicológicas da Faculdade de Ciências Farmacêuticas da Universidade de São Paulo, São Paulo, Brazil

    D Vivona

  8. Department of Hematology, Nephrology, and Rheumatology, Akita University Graduate School of Medicine, Akita, Japan

    N Takahashi

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Correspondence to J Cao.

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Competing interests

Dr Naoto Takahashi reports grants, personal fees from Novartis, Bristol-Myers Squibb and Pfizer, outside the submitted work. The remaining authors declare no conflict of interest.

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Zheng, Q., Wu, H., Yu, Q. et al. ABCB1 polymorphisms predict imatinib response in chronic myeloid leukemia patients: a systematic review and meta-analysis. Pharmacogenomics J 15, 127–134 (2015). https://doi.org/10.1038/tpj.2014.54

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