{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:45:38Z","timestamp":1787013938530,"version":"build-2736575974"},"reference-count":38,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2022,8,12]],"date-time":"2022-08-12T00:00:00Z","timestamp":1660262400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["15K18932"],"award-info":[{"award-number":["15K18932"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["26253041"],"award-info":[{"award-number":["26253041"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"published-print":{"date-parts":[[2022,10]]},"abstract":"<jats:title>Summary<\/jats:title>\n                  <jats:p>\n                    Inherited genetic variation is associated with 6\u2010mercaptopurine (6\u2010MP) dose reduction and frequent toxicities induced by 6\u2010MP. However, the tolerable dose for 6\u2010MP is not fully predicted by the known variation in\n                    <jats:italic>NUDT15<\/jats:italic>\n                    and\n                    <jats:italic>TPMT<\/jats:italic>\n                    among Asian children with acute lymphoblastic leukaemia (ALL). We performed a genome\u2010wide association study (GWAS) related to 6\u2010MP dose among Japanese children with ALL. This GWAS comprised 224 patients previously enrolled in Tokyo Children's Cancer Study Group clinical studies with replication attempted in 55 patients. Genome\u2010wide single nucleotide polymorphism (SNP) genotypes were evaluated for association with average 6\u2010MP dose during the initial 168\u2009days of maintenance therapy. Possible associations were observed across five gene\u2010coding regions, among which only variants at 13q14.2 were significant and replicated genome\u2010wide (rs116855232,\n                    <jats:italic>NUDT15<\/jats:italic>\n                    ,\n                    <jats:italic>\u03b2<\/jats:italic>\n                    \u00a0=\u00a0\u221210.99,\n                    <jats:italic>p<\/jats:italic>\n                    \u00a0=\u00a03.7\u2009\u00d7\u200910\n                    <jats:sup>\u221213<\/jats:sup>\n                    ). Notable findings were observed for variants in\n                    <jats:italic>AFF3<\/jats:italic>\n                    (rs75364948,\n                    <jats:italic>p<\/jats:italic>\n                    \u00a0=\u00a02.05\u2009\u00d7\u200910\n                    <jats:sup>\u22126<\/jats:sup>\n                    ) and\n                    <jats:italic>CHST11<\/jats:italic>\n                    (rs1148407,\n                    <jats:italic>p<\/jats:italic>\n                    \u00a0=\u00a02.09\u2009\u00d7\u200910\n                    <jats:sup>\u22126<\/jats:sup>\n                    ), but were not replicated possibly due to small numbers. A previously reported candidate SNP in\n                    <jats:italic>MTHFR<\/jats:italic>\n                    was associated with higher average 6\u2010MP dose (rs1801133,\n                    <jats:italic>p<\/jats:italic>\n                    \u00a0=\u00a00.045), and\n                    <jats:italic>FOLH1<\/jats:italic>\n                    (rs12574928) was associated in an evaluation of candidate regions (\n                    <jats:italic>p<\/jats:italic>\n                    <jats:sub>adjust<\/jats:sub>\n                    \u00a0=\u00a00.013). This study provides strong evidence that rs116855232 in\n                    <jats:italic>NUDT15<\/jats:italic>\n                    is the genetic factor predominantly associated with 6\u2010MP tolerable dose in children in Japan.\n                  <\/jats:p>","DOI":"10.1111\/bjh.18405","type":"journal-article","created":{"date-parts":[[2022,8,12]],"date-time":"2022-08-12T22:13:27Z","timestamp":1660342407000},"page":"260-269","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Prominence of\n                    <i>NUDT15<\/i>\n                    genetic variation associated with 6\u2010mercaptopurine tolerance in a genome\u2010wide association study of Japanese children with acute lymphoblastic leukaemia"],"prefix":"10.1111","volume":"199","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8949-1293","authenticated-orcid":false,"given":"Yoichi","family":"Tanaka","sequence":"first","affiliation":[{"name":"Division of Medical Safety Sciences National Institute of Health Sciences  Kanagawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1360-9531","authenticated-orcid":false,"given":"Kevin Y.","family":"Urayama","sequence":"additional","affiliation":[{"name":"Graduate School of Public Health St. Luke's International University  Tokyo Japan"},{"name":"Department of Social Medicine National Center for Child Health and Development  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makiko","family":"Mori","sequence":"additional","affiliation":[{"name":"Department of Hematology\/Oncology Saitama Children's Medical Center  Saitama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Arakawa","sequence":"additional","affiliation":[{"name":"Department of Hematology\/Oncology Saitama Children's Medical Center  Saitama 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