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Iranian Journal of Blood and Cancer، جلد ۱۴، شماره ۲، صفحات ۷۵-۸۴
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عنوان انگلیسی NUDT15 genetic variants and 6-mercaptopurine intolerance in pediatric acute lymphoblastic leukemia: an updated review
چکیده انگلیسی مقاله 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.
کلیدواژه‌های انگلیسی مقاله 6-Mercaptopurine, NUDT15, Leukopenia, polymorphism, pediatric, acute lymphoblastic leukemia
نویسندگان مقاله | Payam Siyadat
Department of Hematology, School of Allied Medical Sciences, Iran University of Medical Sciences, Tehran, Iran


| Ehsan Yazdandoust
Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran


| Maryam Sheikhi
Cancer Molecular Pathology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran


| Hossein Ayatollahi
Cancer Molecular Pathology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
نشانی اینترنتی http://ijbc.ir/browse.php?a_code=A-10-693-1&slc_lang=en&sid=1
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کد مقاله (doi)
زبان مقاله منتشر شده en
موضوعات مقاله منتشر شده Pediatric Hematology & Oncology
نوع مقاله منتشر شده مقاله مروری
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