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MTHFR polymorphisms in childhood acute lymphoblastic leukemia: influence on methotrexate therapy

Authors Umerez M, Gutierrez-Camino Á, Muñoz-Maldonado C, Martin-Guerrero I, Garcia-Orad A

Received 14 December 2016

Accepted for publication 17 February 2017

Published 27 March 2017 Volume 2017:10 Pages 69—78

DOI https://doi.org/10.2147/PGPM.S107047

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Akshita Wason

Peer reviewer comments 2

Editor who approved publication: Dr Martin Bluth


Maitane Umerez,1 Ángela Gutierrez-Camino,1 Carmen Muñoz-Maldonado,1 Idoia Martin-Guerrero,1 Africa Garcia-Orad1,2

1Department of Genetics, Physical Anthropology and Animal Physiology, Faculty of Medicine and Nursery, University of the Basque Country, UPV/EHU, Leioa, 2BioCruces Health Research Institute, Barakaldo, Spain

Abstract: Methotrexate (MTX) is an important component in the therapy used to treat childhood acute lymphoblastic leukemia (ALL). Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme for MTX pharmacokinetics. Two single-nucleotide polymorphisms in MTHFR gene, C677T and A1298C, affecting MTHFR activity, have been widely studied as potential markers of MTX toxicity and/or outcome in pediatric ALL. In this review, we show that the majority of published reports do not find association or present opposite effect. Therefore, MTHFR C677T and A1298C polymorphisms do not seem to be good markers of MTX-related toxicity and/or outcome in pediatric ALL. The efforts should be focused on other genes, such as transporter genes or microRNA-related genes.

Keywords: MTHFR, methotrexate, toxicity, outcome, C677T, A1298C

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