{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T03:22:59Z","timestamp":1789010579735,"version":"build-2803163510"},"reference-count":20,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2015,6,2]],"date-time":"2015-06-02T00:00:00Z","timestamp":1433203200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"published-print":{"date-parts":[[2015,10]]},"abstract":"Summary<\/jats:title>\n \n Genotyping of\n \n TPMT<\/jats:styled-content>\n <\/jats:italic>\n prior to 6\u2010mercaptopurine (6\u2010\n MP<\/jats:styled-content>\n ) administration in acute lymphoblastic leukaemia (\n ALL<\/jats:styled-content>\n ) patients has been integrated into clinical practice in some populations of European ancestry. However, the comparable rates of 6\u2010\n MP<\/jats:styled-content>\n myelotoxicity, but rarity of\n \n TPMT<\/jats:styled-content>\n <\/jats:italic>\n variants, in Asians suggest that major determinants have yet to be discovered in this population. We genotyped 92 Japanese paediatric\n ALL<\/jats:styled-content>\n patients for\n \n NUDT<\/jats:styled-content>\n 15\n <\/jats:italic>\n rs116855232, a 6\u2010\n MP<\/jats:styled-content>\n toxicity\u2010related locus discovered in Asians. Logistic regression and survival analysis were used to evaluate its association with leucopenia, hepatotoxicity, 6\u2010\n MP<\/jats:styled-content>\n dose reduction, therapy interruption and event\u2010free survival. The allele frequency of rs116855232 was 0\u00b716, and leucopenia was more common in carriers of the T allele (odds ratio, 7\u00b720; 95% confidence interval, 2\u00b749\u201320\u00b780;\n P\u00a0<\/jats:italic>\n =\n \u00a0<\/jats:italic>\n 2\u00b77\u00a0\u00d7\u00a010\n \u22124<\/jats:sup>\n ). As leucopenia results in 6\u2010\n MP<\/jats:styled-content>\n dose reduction, we observed average doses during maintenance therapy of 40\u00b77, 29\u00b73 and 8\u00b78\u00a0mg\/m\n 2<\/jats:sup>\n for patients with\n CC<\/jats:styled-content>\n ,\n CT<\/jats:styled-content>\n and\n TT<\/jats:styled-content>\n genotypes, respectively (\n P\u00a0<\/jats:italic>\n <\n \u00a0<\/jats:italic>\n 0\u00b7001). Hepatotoxicity was observed only in\n CC<\/jats:styled-content>\n genotype patients. Event\u2010free survival did not significantly differ by\n \n NUDT<\/jats:styled-content>\n 15\n <\/jats:italic>\n genotype. rs116855232 is an important determinant of 6\u2010\n MP<\/jats:styled-content>\n myelotoxicity in Japanese children with\n ALL<\/jats:styled-content>\n and may represent the most robust toxicity\u2010related locus in Asians to date. Considerations for clinical application may be warranted.\n <\/jats:p>","DOI":"10.1111\/bjh.13518","type":"journal-article","created":{"date-parts":[[2015,6,2]],"date-time":"2015-06-02T19:41:55Z","timestamp":1433274115000},"page":"109-115","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":117,"title":["Susceptibility to 6\u2010\n MP<\/scp>\n toxicity conferred by a\n \n NUDT<\/scp>\n 15\n <\/i>\n variant in Japanese children with acute lymphoblastic leukaemia"],"prefix":"10.1111","volume":"171","author":[{"given":"Yoichi","family":"Tanaka","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacy Centre for Clinical Pharmacy and Sciences School of Pharmacy Kitasato University Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Motohiro","family":"Kato","sequence":"additional","affiliation":[{"name":"Department of Paediatrics The University of Tokyo Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daisuke","family":"Hasegawa","sequence":"additional","affiliation":[{"name":"Department of Paediatrics St. Luke's International Hospital Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin Y.","family":"Urayama","sequence":"additional","affiliation":[{"name":"Department of Human Genetics and Disease Diversity Tokyo Medical and Dental University Tokyo Japan"},{"name":"Centre for Clinical Epidemiology St. Luke's Life Science Institute Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hisaya","family":"Nakadate","sequence":"additional","affiliation":[{"name":"Department of General Paediatrics & Interdisciplinary Medicine National Centre for Child Health and Development Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kensuke","family":"Kondoh","sequence":"additional","affiliation":[{"name":"Department of Paediatrics St. Marianna University School of Medicine Kanagawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kozue","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Department of Paediatrics Teikyo University Hospital Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsuyoshi","family":"Koh","sequence":"additional","affiliation":[{"name":"Department of Haematology\/Oncology Saitama Children's Medical Centre Saitama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takako","family":"Komiyama","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy Centre for Clinical Pharmacy and Sciences School of Pharmacy Kitasato University Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Manabe","sequence":"additional","affiliation":[{"name":"Department of Paediatrics St. Luke's International Hospital Tokyo 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