en Pediatric Hematology & Oncology Pediatric Hematology & Oncology مقاله مروری Review Article <div style="text-align: justify;"><span style="line-height:2;"><span style="font-family:Arial;"><span style="font-size:14px;">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&ndash;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.</span></span></span></div> 6-Mercaptopurine, NUDT15, Leukopenia, polymorphism, pediatric, acute lymphoblastic leukemia 75 84 http://ijbc.ir/browse.php?a_code=A-10-693-1&slc_lang=en&sid=1 Payam Siyadat payam.siyadat19899@gmail.com 10031947532846008963 10031947532846008963 No Department of Hematology, School of Allied Medical Sciences, Iran University of Medical Sciences, Tehran, Iran Ehsan Yazdandoust yazdandouste@gmail.com 10031947532846008964 10031947532846008964 No Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran Maryam Sheikhi sheikhim75@gmail.com 10031947532846008965 10031947532846008965 No Cancer Molecular Pathology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran Hossein Ayatollahi ayatollahihossein@yahoo.com 10031947532846008966 10031947532846008966 Yes Cancer Molecular Pathology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran