{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T18:58:18Z","timestamp":1790621898722,"version":"4.1.0"},"reference-count":50,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T00:00:00Z","timestamp":1780617600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T00:00:00Z","timestamp":1780617600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Br J Clin Pharmacol"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>This study aimed to investigate the real\u2010world profiles of 6\u2010mercaptopurine (6\u2010MP) treatment in various TPMT\/NUDT15 phenotype groups among paediatric patients with ALL.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We conducted a prospective cohort study of 104 paediatric patients with ALL during the maintenance phase, collecting baseline data and following up monthly for 5\u2009months. Patients were genotyped and classified as normal (NM), intermediate (IM) or poor (PM) metabolizers based on the\n                      <jats:italic>TPMT<\/jats:italic>\n                      and\n                      <jats:italic>NUDT15<\/jats:italic>\n                      genetic variations. Additionally, TPMT activity and metabolite concentrations (6\u2010thioguanine nucleotides; 6\u2010TGN and 6\u2010methylmercaptopurine nucleotides; 6\u2010MMPN) were also quantified.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The patients were categorized into five TPMT\/NUDT15 phenotype groups: NM\/NM (73.08%), NM\/IM (17.31%), NM\/PM (1.92%), IM\/NM (3.85%) and IM\/IM (3.85%). The tolerated 6\u2010MP dose was lowest in the NM\/PM group (18\u2009mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      , IQR\u2009=\u20098\u201329\u2009mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      ) and IM\/IM group (25\u2009mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      , IQR\u2009=\u20098\u201326\u2009mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      ). The IM\/IM had the highest rate of early neutropenia (75%). TPMT activity remained stable throughout the study except in the NM\/PM group, which showed significant fluctuations. Patients with NM\/PM had the lowest 6\u2010TGN level, and patients with IM\/NM showed high 6\u2010TGN levels. Patients with NM\/NM and NM\/IM exhibited elevated levels of 6\u2010MMPN, which were associated with the occurrence of hepatotoxicity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      The\n                      <jats:italic>TPMT<\/jats:italic>\n                      and\n                      <jats:italic>NUDT15<\/jats:italic>\n                      genes influence the side effects of 6\u2010MP medications. Patients who have variations in both genes are at a higher risk of experiencing toxicity. High levels of 6\u2010TGN are associated with\n                      <jats:italic>TPMT<\/jats:italic>\n                      variants, whereas low levels are linked to\n                      <jats:italic>NUDT15<\/jats:italic>\n                      variants. This could facilitate more precise monitoring of toxicity.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/bcp.70634","type":"journal-article","created":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T03:30:55Z","timestamp":1780716655000},"page":"3437-3447","source":"Crossref","is-referenced-by-count":0,"title":["6\u2010Mercaptopurine metabolic profiles and clinical outcomes in TPMT and NUDT15 phenotypes during maintenance therapy for Thai paediatric acute lymphoblastic leukaemia"],"prefix":"10.1002","volume":"92","author":[{"given":"Angkana","family":"Winaichatsak","sequence":"first","affiliation":[{"name":"Department of Pediatrics Maharat Nakhon Ratchasima Hospital  Nakhon Ratchasima Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samart","family":"Pakakasama","sequence":"additional","affiliation":[{"name":"Division of Hematology\u2010Oncology, Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol 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