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Influence of ABCB1 polymorphisms upon the effectiveness of standard treatment for acute myeloid leukemia: A systematic review and meta-analysis of observational studies

The Pharmacogenomics Journal volume 15, pages 109–118 (2015)Cite this article

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Abstract

The ABCB1 gene encodes for P-glycoprotein (P-gp), an efflux pump for a variety of xenobiotics. The role of ABCB1 polymorphisms in acute myeloid leukemia (AML) outcomes of standard chemotherapy (cytarabine plus anthracyclines) remains controversial. A systematic search was made of studies evaluating the association between ABCB1 polymorphisms 1236C>T, 2677G>T/A and 3435C>T and effectiveness variables. We found seven cohort studies (1241 patients) showing a significantly higher overall survival (OS) among carriers of the variant allele of 1236C>T at year 4 (odds ratio (OR): 1.47, 95% confidence interval (CI): 1.07–2.01), 2677G>T/A at years 4–5 (OR: 1.37, 95% CI: 1.01–1.86) and 3435C>T at years 3 (OR: 1.41, 95% CI: 1.03–1.94) and 4–5 (OR: 1.42, 95% CI: 1.05–1.91). In the subgroup analysis according to ethnicity, Caucasians carrying variant allele showed consistent results in OS. ABCB1 influence upon complete remission could not be demonstrated. Future studies based on larger populations and multiethnic groups should help clarify the effect of P-gp polymorphisms upon other outcomes.

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Acknowledgements

Work supported by grant of the Pharmacy and Hematology Departments and the Pharmacogenetic Unit of ‘Instituto Investigación Sanitaria La Fe’ and ‘Área del Medicamento’ of ‘Hospital Universitari i Politècnic La Fe’, Valencia, Spain. This study was supported in part by research funding from the ‘Instituto Carlos III’ grant’ PIE13/00046’ and ‘Instituto Investigación Sanitaria La Fe’ 2013/0331.

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Authors and Affiliations

  1. Unidad de Farmacogenética, Instituto Investigación Sanitaria La Fe and Área del Medicamento Hospital Universitario y Politécnico La Fe. Av. Fernando Abril Martorell, Valencia, Spain

    J E Megías-Vericat, L Rojas, M J Herrero, V Bosó & S F Aliño

  2. Servicio de Farmacia, Área del Medicamento, Hospital Universitario y Politécnico La Fe. Av. Fernando Abril Martorell, Valencia, Spain

    J E Megías-Vericat, V Bosó & J L Poveda

  3. Department of Internal Medicine, Faculty of Medicine, Pontificia Universidad Católica de Chile, Av. Libertador Bernardo O Higgins, Santiago, Chile

    L Rojas

  4. Departamento Farmacología, Facultad de Medicina, Universidad de Valencia, Av. Blasco Ibáñez, Valencia, Spain

    M J Herrero & S F Aliño

  5. Servicio de Hematología y Hemoterapia, Hospital Universitario y Politécnico La Fe. Av. Fernando Abril Martorell, Valencia, Spain

    P Montesinos, F Moscardó & M Á Sanz

  6. Unidad de Farmacología Clínica, Área del Medicamento, Hospital Universitario y Politécnico La Fe. Av. Fernando Abril Martorell, Valencia, Spain

    S F Aliño

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Megías-Vericat, J., Rojas, L., Herrero, M. et al. Influence of ABCB1 polymorphisms upon the effectiveness of standard treatment for acute myeloid leukemia: A systematic review and meta-analysis of observational studies. Pharmacogenomics J 15, 109–118 (2015). https://doi.org/10.1038/tpj.2014.80

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