{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T14:08:54Z","timestamp":1785766134955,"version":"3.56.0"},"reference-count":36,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T00:00:00Z","timestamp":1768953600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T00:00:00Z","timestamp":1768953600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The nucleoside diphosphate\u2010linked moiety X\u2010type motif 15 (\n                    <jats:italic>NUDT15<\/jats:italic>\n                    ) has been identified as a key genetic determinant of 6\u2010mercaptopurine (6\u2010MP)\u2010induced hematopoietic toxicity in populations with a high frequency of\n                    <jats:italic>NUDT15<\/jats:italic>\n                    variants but a low frequency of thiopurine S\u2010methyltransferase (\n                    <jats:italic>TPMT<\/jats:italic>\n                    ) variants. However, evidence remains limited in populations where both genetic variants are prevalent. This study aimed to characterize the impact of\n                    <jats:italic>NUDT15<\/jats:italic>\n                    and\n                    <jats:italic>TPMT<\/jats:italic>\n                    polymorphisms on 6\u2010MP\u2010induced hematopoietic toxicity in Thai pediatric patients, a population with a high prevalence of both variants. A total of 215 Thai pediatric patients undergoing maintenance\u2010phase therapy with 6\u2010MP were enrolled. Genotyping for\n                    <jats:italic>TPMT<\/jats:italic>\n                    and\n                    <jats:italic>NUDT15<\/jats:italic>\n                    was performed, and phenotypes were determined based on the genotype data. The results showed that the absolute neutrophil count (ANC), white blood cell (WBC) count, and platelet count during the first 6\u2009months of the maintenance phase were significantly lower in intermediate metabolizers (IM) of NUDT15 compared to normal metabolizers (NM). The risk of 6\u2010MP\u2010induced severe neutropenia increased by 6.8\u201324.5\u2010fold in IM\/PM of NUDT15. The suitable tolerance doses of 6\u2010MP in the IM\/PM of NUDT15 were lower than the normal starting dose while the tolerance dose of 6\u2010MP in the indeterminate metabolizers (IDM) of NUDT15 or IM of TPMT was not significantly different from the normal starting dose. In conclusion,\n                    <jats:italic>NUDT15<\/jats:italic>\n                    plays a more prominent role than\n                    <jats:italic>TPMT<\/jats:italic>\n                    in 6\u2010MP\u2010induced hematopoietic toxicity in Thai pediatric patients. Determining NUDT15 phenotypes is essential to ensure appropriate 6\u2010MP dosage adjustments and to mitigate the risk of severe hematopoietic toxicity in this population.\n                  <\/jats:p>","DOI":"10.1111\/cts.70480","type":"journal-article","created":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T09:05:39Z","timestamp":1768986339000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Genetic Determinants of Hematopoietic Toxicity Risk in Thai Pediatric Patients Undergoing 6\u2010Mercaptopurine Treatment"],"prefix":"10.1111","volume":"19","author":[{"given":"Kanyarat","family":"Khaeso","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine Khon Kaen University  Khon Kaen Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Su\u2010on","family":"Chainansamit","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Khon Kaen Hospital  Khon Kaen Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pitchayanan","family":"Kuwatjanakul","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Udon Thani Hospital  Udon Thani Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patcharee","family":"Komvilaisak","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Faculty of Medicine Khon Kaen University  Khon Kaen Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1631-3178","authenticated-orcid":false,"given":"Nontaya","family":"Nakkam","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine Khon Kaen University  Khon Kaen Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kunanya","family":"Suwannaying","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Faculty of Medicine Khon Kaen University  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