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A systematic review and meta-analysis of the impact of WT1 polymorphism rs16754 in the effectiveness of standard chemotherapy in patients with acute myeloid leukemia

The Pharmacogenomics Journal volume 16, pages 30–40 (2016)Cite this article

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Abstract

The polymorphism rs16754 of the WT1 gene has been described as a possible prognostic marker in different acute myeloid leukemia (AML) cohorts; however, it is not supported by all the studies. We performed the first meta-analysis evaluating the effect of this polymorphism upon the effectiveness of standard AML therapy. Fourteen cohort studies were included (3618 patients). Patients with the variant allele showed a significant higher overall survival (OS) at 5 years (OR:1.24, 95% CI: 1.06–1.45, P=0.007, with dominant model). WT1 did not influence complete remission, but a higher disease-free survival was observed with the variant allele. In the subgroup analysis, Caucasians, pediatric and patients treated with idarubicin and etoposide carrying the variant allele showed consistent results in OS, whereas patients with cytogenetically normal AML did not show differences. To verify the effect of this polymorphism upon other outcomes, studies in larger and multiracial populations are needed.

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Acknowledgements

This study was supported by grants from the ‘Instituto Carlos III’ (PIE13/00046) and the ‘Instituto Investigación Sanitaria La Fe’ (2013/0331) granted to Pharmacy and Hematology Departments and the Pharmacogenetics Unit of the ‘Instituto Investigación Sanitaria La Fe’ and the ‘Área del Medicamento’ of the ‘Hospital Universitari i Politècnic La Fe’, Valencia, Spain. We are grateful to Adrian Keukens for his editorial assistance on this manuscript.

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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, Valencia, Spain

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

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

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

  3. Departamento Farmacología, Facultad de Medicina, Universidad de Valencia, Valencia, Spain

    M J Herrero & S F Aliño

  4. Department of Internal Medicine, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile

    L Rojas

  5. Servicio de Hematología y Hemoterapia, Hospital Universitario y Politécnico La Fe, Valencia, Spain

    P Montesinos, F Moscardó, D Martínez-Cuadrón & M Á Sanz

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

    S F Aliño

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  1. J E Megías-Vericat
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Correspondence to J E Megías-Vericat or M J Herrero.

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Megías-Vericat, J., Herrero, M., Rojas, L. et al. A systematic review and meta-analysis of the impact of WT1 polymorphism rs16754 in the effectiveness of standard chemotherapy in patients with acute myeloid leukemia. Pharmacogenomics J 16, 30–40 (2016). https://doi.org/10.1038/tpj.2015.80

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