{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T22:32:57Z","timestamp":1793226777670,"version":"4.5.0"},"reference-count":34,"publisher":"Elsevier BV","issue":"10","license":[{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2017YFC0909300"],"award-info":[{"award-number":["2017YFC0909300"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013314","name":"Higher Education Discipline Innovation Project","doi-asserted-by":"publisher","award":["B16047"],"award-info":[{"award-number":["B16047"]}],"id":[{"id":"10.13039\/501100013314","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002402","name":"Sun Yat-Sen University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002402","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82474002"],"award-info":[{"award-number":["82474002"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82020108031"],"award-info":[{"award-number":["82020108031"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100017688","name":"Guangdong Provincial Key Laboratory of Construction Foundation","doi-asserted-by":"publisher","award":["2020B1212060034"],"award-info":[{"award-number":["2020B1212060034"]}],"id":[{"id":"10.13039\/501100017688","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100017688","name":"Guangdong Provincial Key Laboratory of Construction Foundation","doi-asserted-by":"publisher","award":["2017B030314030"],"award-info":[{"award-number":["2017B030314030"]}],"id":[{"id":"10.13039\/501100017688","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2025A1515012521"],"award-info":[{"award-number":["2025A1515012521"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2024A1515012445"],"award-info":[{"award-number":["2024A1515012445"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2023A1515010362"],"award-info":[{"award-number":["2023A1515010362"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["dmd.aspetjournals.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Drug Metabolism and Disposition"],"published-print":{"date-parts":[[2025,10]]},"DOI":"10.1016\/j.dmd.2025.100154","type":"journal-article","created":{"date-parts":[[2025,8,29]],"date-time":"2025-08-29T02:23:58Z","timestamp":1756434238000},"page":"100154","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":1,"title":["Effect and mechanism of allopurinol in acute lymphoblastic leukemia maintenance therapy: Reducing hepatotoxicity and improving myelosuppression effect via thiopurine methyltransferase inhibition and increased DNA-thioguanine levels"],"prefix":"10.1016","volume":"53","author":[{"given":"Yanping","family":"Guan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoli","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiaolan","family":"Xuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ailing","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiyu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianpei","family":"Fang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuequn","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhong","family":"Zuo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaoxing","family":"Guan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Libin","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueding","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dunhua","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"3","key":"10.1016\/j.dmd.2025.100154_bib1","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1038\/leu.2017.265","article-title":"Results of NOPHO ALL2008 treatment for patients aged 1-45 years with acute lymphoblastic leukemia","volume":"32","author":"Toft","year":"2018","journal-title":"Leukemia"},{"issue":"3","key":"10.1016\/j.dmd.2025.100154_bib2","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1001\/jamaoncol.2015.0245","article-title":"Systemic exposure to thiopurines and risk of relapse in children with acute lymphoblastic leukemia: a Children's Oncology Group Study","volume":"1","author":"Bhatia","year":"2015","journal-title":"JAMA Oncol"},{"issue":"4","key":"10.1016\/j.dmd.2025.100154_bib3","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.clpt.2003.12.001","article-title":"Methylated metabolites of 6-mercaptopurine are associated with hepatotoxicity","volume":"75","author":"Nygaard","year":"2004","journal-title":"Clin Pharmacol Ther"},{"issue":"7","key":"10.1016\/j.dmd.2025.100154_bib4","doi-asserted-by":"crossref","first-page":"1749","DOI":"10.1038\/s41375-022-01591-4","article-title":"Maintenance therapy for acute lymphoblastic leukemia: basic science and clinical translations","volume":"36","author":"Toksvang","year":"2022","journal-title":"Leukemia"},{"issue":"9","key":"10.1016\/j.dmd.2025.100154_bib5","doi-asserted-by":"crossref","first-page":"2846","DOI":"10.3324\/haematol.2023.284390","article-title":"Effects of allopurinol on 6-mercaptopurine metabolism in unselected patients with pediatric acute lymphoblastic leukemia: a prospective phase II study","volume":"109","author":"Kallstrom","year":"2024","journal-title":"Haematologica"},{"issue":"5","key":"10.1016\/j.dmd.2025.100154_bib6","doi-asserted-by":"crossref","first-page":"1246","DOI":"10.1080\/10428194.2019.1702183","article-title":"Use of allopurinol to reduce hepatotoxicity from 6-mercaptopurine (6-MP) in patients with acute lymphoblastic leukemia (ALL)","volume":"61","author":"Stuckert","year":"2020","journal-title":"Leuk Lymphoma"},{"issue":"11","key":"10.1016\/j.dmd.2025.100154_bib7","doi-asserted-by":"crossref","DOI":"10.1002\/pbc.28360","article-title":"Allopurinol use during pediatric acute lymphoblastic leukemia maintenance therapy safely corrects skewed 6-mercaptopurine metabolism, improving inadequate myelosuppression and reducing gastrointestinal toxicity","volume":"67","author":"Cohen","year":"2020","journal-title":"Pediatr Blood Cancer"},{"key":"10.1016\/j.dmd.2025.100154_bib8","doi-asserted-by":"crossref","first-page":"176","DOI":"10.12688\/f1000research.17760.2","article-title":"Allopurinol reverses mercaptopurine-induced hypoglycemia in patients with acute lymphoblastic leukemia","volume":"8","author":"Zhang","year":"2019","journal-title":"F1000Research"},{"issue":"4","key":"10.1016\/j.dmd.2025.100154_bib9","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1016\/j.bcp.2013.06.002","article-title":"Mechanism of allopurinol induced TPMT inhibition","volume":"86","author":"Blaker","year":"2013","journal-title":"Biochem Pharmacol"},{"issue":"1","key":"10.1016\/j.dmd.2025.100154_bib10","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1038\/nrc2292","article-title":"Thiopurines in current medical practice: molecular mechanisms and contributions to therapy-related cancer","volume":"8","author":"Karran","year":"2008","journal-title":"Nat Rev Cancer"},{"issue":"4","key":"10.1016\/j.dmd.2025.100154_bib11","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1016\/S1470-2045(17)30154-7","article-title":"DNA-thioguanine nucleotide concentration and relapse-free survival during maintenance therapy of childhood acute lymphoblastic leukaemia (NOPHO ALL2008): a prospective substudy of a phase 3 trial","volume":"18","author":"Nielsen","year":"2017","journal-title":"Lancet Oncol"},{"issue":"4","key":"10.1016\/j.dmd.2025.100154_bib12","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1038\/ng.3508","article-title":"NUDT15 polymorphisms alter thiopurine metabolism and hematopoietic toxicity","volume":"48","author":"Moriyama","year":"2016","journal-title":"Nat Genet"},{"issue":"3","key":"10.1016\/j.dmd.2025.100154_bib13","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1097\/MPH.0000000000002117","article-title":"Allopurinol to prevent mercaptopurine adverse effects in children and young adults with acute lymphoblastic leukemia","volume":"43","author":"Kamojjala","year":"2021","journal-title":"J Pediatr Hematol Oncol"},{"issue":"2","key":"10.1016\/j.dmd.2025.100154_bib14","article-title":"Assessment on the use of allopurinol to improve safety and efficacy of mercaptopurine in pediatric patients with acute lymphoblastic leukemia and lymphoma during maintenance therapy","volume":"7","author":"Barone","year":"2024","journal-title":"Cancer Rep"},{"key":"10.1016\/j.dmd.2025.100154_bib15","doi-asserted-by":"crossref","DOI":"10.3389\/fonc.2021.797194","article-title":"Prognostic value and outcome for ETV6\/RUNX1-positive pediatric acute lymphoblastic leukemia: a report from the South China Children's Leukemia Group","volume":"11","author":"Qiu","year":"2021","journal-title":"Front Oncol"},{"issue":"2","key":"10.1016\/j.dmd.2025.100154_bib16","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1111\/j.1365-2125.2004.02113.x","article-title":"Phenotyping and genotyping study of thiopurine S-methyltransferase in healthy Chinese children: a comparison of Han and Yao ethnic groups","volume":"58","author":"Zhang","year":"2004","journal-title":"Br J Clin Pharmacol"},{"issue":"9","key":"10.1016\/j.dmd.2025.100154_bib17","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1111\/apt.13796","article-title":"NUDT15 polymorphisms are better than thiopurine S-methyltransferase as predictor of risk for thiopurine-induced leukopenia in Chinese patients with Crohn's disease","volume":"44","author":"Zhu","year":"2016","journal-title":"Aliment Pharmacol Ther"},{"issue":"6","key":"10.1016\/j.dmd.2025.100154_bib18","doi-asserted-by":"crossref","first-page":"1236","DOI":"10.1002\/cpt.2730","article-title":"DNA-thioguanine nucleotides as a marker for thiopurine induced late leukopenia after dose optimizing by NUDT15 C415T in Chinese patients with IBD","volume":"112","author":"Zhu","year":"2022","journal-title":"Clin Pharmacol Ther"},{"issue":"5","key":"10.1016\/j.dmd.2025.100154_bib19","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1093\/jnci\/djae004","article-title":"Additive effects of TPMT and NUDT15 on thiopurine toxicity in children with acute lymphoblastic leukemia across multiethnic populations","volume":"116","author":"Maillard","year":"2024","journal-title":"J Natl Cancer Inst"},{"issue":"23","key":"10.1016\/j.dmd.2025.100154_bib20","doi-asserted-by":"crossref","first-page":"2001","DOI":"10.1093\/jnci\/91.23.2001","article-title":"Mercaptopurine therapy intolerance and heterozygosity at the thiopurine S-methyltransferase gene locus","volume":"91","author":"Relling","year":"1999","journal-title":"J Natl Cancer Inst"},{"issue":"6","key":"10.1016\/j.dmd.2025.100154_bib21","doi-asserted-by":"crossref","first-page":"1326","DOI":"10.1002\/cpt.2894","article-title":"Thiopurine methyltransferase intermediate metabolizer status determines thiopurine-associated toxicity during maintenance therapy in childhood acute lymphoblastic leukemia","volume":"113","author":"Schwarz","year":"2023","journal-title":"Clin Pharmacol Ther"},{"issue":"12","key":"10.1016\/j.dmd.2025.100154_bib22","doi-asserted-by":"crossref","first-page":"2104","DOI":"10.1002\/pbc.26139","article-title":"Maintenance therapy of childhood acute lymphoblastic leukemia revisited: should drug doses be adjusted by white blood cell, neutrophil, or lymphocyte counts?","volume":"63","author":"Schmiegelow","year":"2016","journal-title":"Pediatr Blood Cancer"},{"issue":"7","key":"10.1016\/j.dmd.2025.100154_bib23","doi-asserted-by":"crossref","first-page":"1332","DOI":"10.1200\/JCO.2003.04.039","article-title":"Intensification of mercaptopurine\/methotrexate maintenance chemotherapy may increase the risk of relapse for some children with acute lymphoblastic leukemia","volume":"21","author":"Schmiegelow","year":"2003","journal-title":"J Clin Oncol"},{"issue":"2","key":"10.1016\/j.dmd.2025.100154_bib24","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1111\/bjh.13240","article-title":"Thiopurine dose intensity and treatment outcome in childhood lymphoblastic leukaemia: the influence of thiopurine methyltransferase pharmacogenetics. Article","volume":"169","author":"Lennard","year":"2015","journal-title":"Br J Haematol"},{"issue":"19","key":"10.1016\/j.dmd.2025.100154_bib25","doi-asserted-by":"crossref","first-page":"2469","DOI":"10.1200\/JCO.2012.47.0500","article-title":"Second malignant neoplasms after treatment of childhood acute lymphoblastic leukemia","volume":"31","author":"Schmiegelow","year":"2013","journal-title":"J Clin Oncol"},{"issue":"4","key":"10.1016\/j.dmd.2025.100154_bib26","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1007\/s002800050816","article-title":"Pharmacokinetics and metabolism of thiopurines in children with acute lymphoblastic leukemia receiving 6-thioguanine versus 6-mercaptopurine","volume":"42","author":"Erb","year":"1998","journal-title":"Cancer Chemother Pharmacol"},{"issue":"3","key":"10.1016\/j.dmd.2025.100154_bib27","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1038\/leu.2008.316","article-title":"Thiopurine methyltransferase activity is related to the risk of relapse of childhood acute lymphoblastic leukemia: results from the NOPHO ALL-92 study","volume":"23","author":"Schmiegelow","year":"2009","journal-title":"Leukemia"},{"issue":"4","key":"10.1016\/j.dmd.2025.100154_bib28","first-page":"601","article-title":"Thiopurine pharmacogenetics: clinical and molecular studies of thiopurine methyltransferase","volume":"29","author":"Weinshilboum","year":"2001","journal-title":"Drug Metab Dispos"},{"issue":"4","key":"10.1016\/j.dmd.2025.100154_bib29","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1002\/pbc.25841","article-title":"Maintenance treatment with low-dose mercaptopurine in combination with allopurinol in children with acute lymphoblastic leukemia and mercaptopurine-induced pancreatitis","volume":"63","author":"Zerra","year":"2016","journal-title":"Pediatr Blood Cancer"},{"issue":"2","key":"10.1016\/j.dmd.2025.100154_bib30","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1097\/MPH.0000000000000499","article-title":"Allopurinol use during maintenance therapy for acute lymphoblastic leukemia avoids mercaptopurine related hepatotoxicity","volume":"38","author":"Giamanco","year":"2016","journal-title":"J Pediatr Hematol Oncol"},{"issue":"11","key":"10.1016\/j.dmd.2025.100154_bib31","doi-asserted-by":"crossref","first-page":"2824","DOI":"10.3324\/haematol.2020.278166","article-title":"Increments in DNA-thioguanine level during thiopurine-enhanced maintenance therapy of acute lymphoblastic leukemia","volume":"106","author":"Larsen","year":"2021","journal-title":"Haematologica"},{"issue":"5","key":"10.1016\/j.dmd.2025.100154_bib32","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1002\/cpt.2716","article-title":"Implementation of NUDT15 genotyping to prevent azathioprine-induced leukopenia for patients with autoimmune disorders in Chinese population","volume":"112","author":"Wang","year":"2022","journal-title":"Clin Pharmacol Ther"},{"issue":"10","key":"10.1016\/j.dmd.2025.100154_bib33","doi-asserted-by":"crossref","first-page":"5394","DOI":"10.1073\/pnas.1915680117","article-title":"Massively parallel variant characterization identifies NUDT15 alleles associated with thiopurine toxicity","volume":"117","author":"Suiter","year":"2020","journal-title":"Proc Natl Acad Sci USA"},{"issue":"10","key":"10.1016\/j.dmd.2025.100154_bib34","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1080\/17425255.2021.1974398","article-title":"Understanding thiopurine methyltransferase polymorphisms for the targeted treatment of hematologic malignancies","volume":"17","author":"Franca","year":"2021","journal-title":"Expert Opin Drug Metab Toxicol"}],"container-title":["Drug Metabolism and Disposition"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0090955625091639?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0090955625091639?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T22:08:04Z","timestamp":1793225284000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0090955625091639"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10]]},"references-count":34,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2025,10]]}},"alternative-id":["S0090955625091639"],"URL":"https:\/\/doi.org\/10.1016\/j.dmd.2025.100154","relation":{},"ISSN":["0090-9556"],"issn-type":[{"value":"0090-9556","type":"print"}],"subject":[],"published":{"date-parts":[[2025,10]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Effect and mechanism of allopurinol in acute lymphoblastic leukemia maintenance therapy: Reducing hepatotoxicity and improving myelosuppression effect via thiopurine methyltransferase inhibition and increased DNA-thioguanine levels","name":"articletitle","label":"Article Title"},{"value":"Drug Metabolism and Disposition","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.dmd.2025.100154","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 American Society for Pharmacology and Experimental Therapeutics. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"100154"}}