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:: Volume 14, Issue 2 (March-2022 2022) ::
IJBC 2022, 14(2): 75-84 Back to browse issues page
NUDT15 genetic variants and 6-mercaptopurine intolerance in pediatric acute lymphoblastic leukemia: an updated review
Payam Siyadat, Ehsan Yazdandoust, Maryam Sheikhi, Hossein Ayatollahi *
Cancer Molecular Pathology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
Abstract:   (447 Views)

Acute lymphoblastic leukemia (ALL) accounts for nearly 30% of pediatric cancers. The maintenance treatment for ALL comprises daily oral 6-mercaptopurine (6-MP) and weekly methotrexate (MTX). 6-MP is a purine analog that can significantly improve the long-term survival of ALL patients. Despite more than 90% of 5-year survival of childhood ALL in developed countries, treatment interruption due to drug toxicities continues to be a grave concern during therapy. Several studies have highlighted the association between some genetic variants and 6-MP toxicities in ALL patients. Some variants of 6-MP metabolizing enzymes received much attention as possible predictors of myelotoxicity following 6-MP therapy. Recently, two landmark genome-wide association studies have highlighted variants in nucleoside diphosphate–linked moiety X-type motif 15 (NUDT15) as promising indicators of 6-MP toxicities. It seems that NUDT15 genotyping can help determine the optimum dose of 6-MP and prevent toxicities, especially fatal myelotoxicity. No association was found between NUDT15 variants and hepatotoxicity or survival rates of ALL patients in previous studies. However, further studies are warranted to shed more light on these issues. The current review updates and evaluates the available scientific data regarding different genetic variants of NUDT15 and their possible roles in 6-MP intolerance in various ethnic groups.

Keywords: 6-Mercaptopurine, NUDT15, Leukopenia, polymorphism, pediatric, acute lymphoblastic leukemia
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: Review Article | Subject: Pediatric Hematology & Oncology
Received: 2021/01/15 | Accepted: 2022/06/4 | Published: 2022/06/28
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Siyadat P, Yazdandoust E, Sheikhi M, Ayatollahi H. NUDT15 genetic variants and 6-mercaptopurine intolerance in pediatric acute lymphoblastic leukemia: an updated review. IJBC 2022; 14 (2) :75-84
URL: http://ijbc.ir/article-1-1109-en.html

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Volume 14, Issue 2 (March-2022 2022) Back to browse issues page
مجله ی خون و سرطان ایران Iranian Journal of Blood and Cancer
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