{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T07:51:14Z","timestamp":1791273074187,"version":"4.1.0"},"reference-count":112,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:00:00Z","timestamp":1791244800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:00:00Z","timestamp":1791244800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"funder":[{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","award":["ZR2025LZL002"],"award-info":[{"award-number":["ZR2025LZL002"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Key Research and Development Program: Key Project on Reproductive Health and Health Protection for Women and Children","award":["2023YFC2706402"],"award-info":[{"award-number":["2023YFC2706402"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Curr. Treat. Options in Oncol."],"published-print":{"date-parts":[[2026,12]]},"DOI":"10.1007\/s11864-026-01415-y","type":"journal-article","created":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T06:59:30Z","timestamp":1791269970000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Personalized Therapy with Mercaptopurine in Acute Lymphoblastic Leukemia: Current Advances and Challenges"],"prefix":"10.1007","volume":"27","author":[{"given":"Haoping","family":"He","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bowei","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqiang","family":"Hao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoyue","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Du","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiwei","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aijun","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,10,6]]},"reference":[{"issue":"27","key":"1415_CR1","doi-asserted-by":"publisher","first-page":"2938","DOI":"10.1200\/jco.2014.59.1636","volume":"33","author":"CH Pui","year":"2015","unstructured":"Pui CH, Yang JJ, Hunger SP, Pieters R, Schrappe M, Biondi A, et al. Childhood Acute Lymphoblastic Leukemia: Progress Through Collaboration. J Clin Oncol. 2015;33(27):2938\u201348. https:\/\/doi.org\/10.1200\/jco.2014.59.1636.","journal-title":"J Clin Oncol"},{"key":"1415_CR2","doi-asserted-by":"publisher","unstructured":"Davis KL, Yao CC, Zimmerman JAO, Rau RE. Immunotherapy in B-cell acute lymphoblastic leukemia. J Natl Compr Canc Netw. 2025;23(12). https:\/\/doi.org\/10.6004\/jnccn.2025.7067.","DOI":"10.6004\/jnccn.2025.7067"},{"issue":"7","key":"1415_CR3","doi-asserted-by":"publisher","first-page":"1749","DOI":"10.1038\/s41375-022-01591-4","volume":"36","author":"LN Toksvang","year":"2022","unstructured":"Toksvang LN, Lee SHR, Yang JJ, Schmiegelow K. Maintenance therapy for acute lymphoblastic leukemia: basic science and clinical translations. Leukemia. 2022;36(7):1749\u201358. https:\/\/doi.org\/10.1038\/s41375-022-01591-4.","journal-title":"Leukemia"},{"issue":"4","key":"1415_CR4","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1016\/j.blre.2015.01.001","volume":"29","author":"L Mei","year":"2015","unstructured":"Mei L, Ontiveros EP, Griffiths EA, Thompson JE, Wang ES, Wetzler M. Pharmacogenetics predictive of response and toxicity in acute lymphoblastic leukemia therapy. Blood Rev. 2015;29(4):243\u20139. https:\/\/doi.org\/10.1016\/j.blre.2015.01.001.","journal-title":"Blood Rev"},{"issue":"4","key":"1415_CR5","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1038\/ng.3508","volume":"48","author":"T Moriyama","year":"2016","unstructured":"Moriyama T, Nishii R, Perez-Andreu V, Yang W, Klussmann FA, Zhao X, et al. NUDT15 polymorphisms alter thiopurine metabolism and hematopoietic toxicity. Nat Genet. 2016;48(4):367\u201373. https:\/\/doi.org\/10.1038\/ng.3508.","journal-title":"Nat Genet"},{"issue":"7","key":"1415_CR6","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1097\/mph.0000000000000206","volume":"36","author":"K Schmiegelow","year":"2014","unstructured":"Schmiegelow K, Nielsen SN, Frandsen TL, Nersting J. Mercaptopurine\/Methotrexate maintenance therapy of childhood acute lymphoblastic leukemia: clinical facts and fiction. J Pediatr Hematol Oncol. 2014;36(7):503\u201317. https:\/\/doi.org\/10.1097\/mph.0000000000000206.","journal-title":"J Pediatr Hematol Oncol"},{"issue":"1","key":"1415_CR7","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1038\/nrc2292","volume":"8","author":"P Karran","year":"2008","unstructured":"Karran P, Attard N. Thiopurines in current medical practice: molecular mechanisms and contributions to therapy-related cancer. Nat Rev Cancer. 2008;8(1):24\u201336. https:\/\/doi.org\/10.1038\/nrc2292.","journal-title":"Nat Rev Cancer"},{"issue":"5","key":"1415_CR8","doi-asserted-by":"publisher","first-page":"607","DOI":"10.1517\/14740338.7.5.607","volume":"7","author":"RW Leong","year":"2008","unstructured":"Leong RW, Gearry RB, Sparrow MP. Thiopurine hepatotoxicity in inflammatory bowel disease: the role for adding allopurinol. Expert Opin Drug Saf. 2008;7(5):607\u201316. https:\/\/doi.org\/10.1517\/14740338.7.5.607.","journal-title":"Expert Opin Drug Saf"},{"issue":"35","key":"1415_CR9","doi-asserted-by":"publisher","first-page":"4027","DOI":"10.2174\/0929867323666160725091915","volume":"23","author":"MG Battelli","year":"2016","unstructured":"Battelli MG, Polito L, Bortolotti M, Bolognesi A. Xanthine Oxidoreductase in Drug Metabolism: Beyond a Role as a Detoxifying Enzyme. Curr Med Chem. 2016;23(35):4027\u201336. https:\/\/doi.org\/10.2174\/0929867323666160725091915.","journal-title":"Curr Med Chem"},{"issue":"6","key":"1415_CR10","doi-asserted-by":"publisher","first-page":"749","DOI":"10.1111\/j.1365-2036.2008.03768.x","volume":"28","author":"A Ansari","year":"2008","unstructured":"Ansari A, Aslam Z, De Sica A, Smith M, Gilshenan K, Fairbanks L, et al. Influence of xanthine oxidase on thiopurine metabolism in Crohn\u2019s disease. Aliment Pharmacol Ther. 2008;28(6):749\u201357. https:\/\/doi.org\/10.1111\/j.1365-2036.2008.03768.x.","journal-title":"Aliment Pharmacol Ther"},{"issue":"5","key":"1415_CR11","doi-asserted-by":"publisher","first-page":"684","DOI":"10.1002\/cpt.540","volume":"101","author":"R Tamm","year":"2017","unstructured":"Tamm R, M\u00e4gi R, Tremmel R, Winter S, Mihailov E, Smid A, et al. Polymorphic variation in TPMT is the principal determinant of TPMT phenotype: A meta-analysis of three genome-wide association studies. Clin Pharmacol Ther. 2017;101(5):684\u201395. https:\/\/doi.org\/10.1002\/cpt.540.","journal-title":"Clin Pharmacol Ther"},{"issue":"5","key":"1415_CR12","doi-asserted-by":"publisher","first-page":"1091","DOI":"10.1002\/cpt.1268","volume":"105","author":"JJ Yang","year":"2019","unstructured":"Yang JJ, Whirl-Carrillo M, Scott SA, Turner AJ, Schwab M, Tanaka Y, et al. Pharmacogene Variation Consortium Gene Introduction: NUDT15. Clin Pharmacol Ther. 2019;105(5):1091\u20134. https:\/\/doi.org\/10.1002\/cpt.1268.","journal-title":"Clin Pharmacol Ther"},{"key":"1415_CR13","doi-asserted-by":"publisher","first-page":"116361","DOI":"10.1016\/j.bcp.2024.116361","volume":"226","author":"H Mu","year":"2024","unstructured":"Mu H, Ye L, Wang B. Detailed resume of S-methyltransferases: Categories, structures, biological functions and research advancements in related pathophysiology and pharmacotherapy. Biochem Pharmacol. 2024;226:116361. https:\/\/doi.org\/10.1016\/j.bcp.2024.116361.","journal-title":"Biochem Pharmacol"},{"issue":"5","key":"1415_CR14","first-page":"651","volume":"32","author":"RM Weinshilboum","year":"1980","unstructured":"Weinshilboum RM, Sladek SL. Mercaptopurine pharmacogenetics: monogenic inheritance of erythrocyte thiopurine methyltransferase activity. Am J Hum Genet. 1980;32(5):651\u201362.","journal-title":"Am J Hum Genet"},{"key":"1415_CR15","doi-asserted-by":"publisher","first-page":"Rrn1236","DOI":"10.1371\/currents.RRN1236","volume":"3","author":"CM Nguyen","year":"2011","unstructured":"Nguyen CM, Mendes MA, Ma JD. Thiopurine methyltransferase (TPMT) genotyping to predict myelosuppression risk. PLoS Curr. 2011;3:Rrn1236. https:\/\/doi.org\/10.1371\/currents.RRN1236.","journal-title":"PLoS Curr"},{"issue":"10","key":"1415_CR16","doi-asserted-by":"publisher","first-page":"1014","DOI":"10.1007\/s00535-010-0248-y","volume":"45","author":"H Ban","year":"2010","unstructured":"Ban H, Andoh A, Imaeda H, Kobori A, Bamba S, Tsujikawa T, et al. The multidrug-resistance protein 4 polymorphism is a new factor accounting for thiopurine sensitivity in Japanese patients with inflammatory bowel disease. J Gastroenterol. 2010;45(10):1014\u201321. https:\/\/doi.org\/10.1007\/s00535-010-0248-y.","journal-title":"J Gastroenterol"},{"issue":"2","key":"1415_CR17","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1111\/bjh.13240","volume":"169","author":"L Lennard","year":"2015","unstructured":"Lennard L, Cartwright CS, Wade R, Vora A. Thiopurine dose intensity and treatment outcome in childhood lymphoblastic leukaemia: the influence of thiopurine methyltransferase pharmacogenetics. Br J Haematol. 2015;169(2):228\u201340. https:\/\/doi.org\/10.1111\/bjh.13240.","journal-title":"Br J Haematol"},{"issue":"2","key":"1415_CR18","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1111\/bjh.14532","volume":"181","author":"AM Soler","year":"2018","unstructured":"Soler AM, Olano N, M\u00e9ndez Y, Lopes A, Silveira A, Dabezies A, et al. TPMT and NUDT15 genes are both related to mercaptopurine intolerance in acute lymphoblastic leukaemia patients from Uruguay. Br J Haematol. 2018;181(2):252\u20135. https:\/\/doi.org\/10.1111\/bjh.14532.","journal-title":"Br J Haematol"},{"key":"1415_CR19","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1186\/1471-2407-14-299","volume":"14","author":"MJ Farfan","year":"2014","unstructured":"Farfan MJ, Salas C, Canales C, Silva F, Villarroel M, Kopp K, et al. Prevalence of TPMT and ITPA gene polymorphisms and effect on mercaptopurine dosage in Chilean children with acute lymphoblastic leukemia. BMC Cancer. 2014;14:299. https:\/\/doi.org\/10.1186\/1471-2407-14-299.","journal-title":"BMC Cancer"},{"issue":"4","key":"1415_CR20","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1111\/bjh.13469","volume":"170","author":"L Lennard","year":"2015","unstructured":"Lennard L, Cartwright CS, Wade R, Vora A. Thiopurine methyltransferase and treatment outcome in the UK acute lymphoblastic leukaemia trial ALL2003. Br J Haematol. 2015;170(4):550\u20138. https:\/\/doi.org\/10.1111\/bjh.13469.","journal-title":"Br J Haematol"},{"issue":"6","key":"1415_CR21","doi-asserted-by":"publisher","first-page":"1326","DOI":"10.1002\/cpt.2894","volume":"113","author":"UI Schwarz","year":"2023","unstructured":"Schwarz UI, Woldanski-Travaglini M, Swanston V, Mikhail M, Cacciotti C, Cairney E, et al. Thiopurine Methyltransferase Intermediate Metabolizer Status and Thiopurine-Associated Toxicity During Maintenance Therapy in Childhood Acute Lymphoblastic Leukemia. Clin Pharmacol Ther. 2023;113(6):1326\u201336. https:\/\/doi.org\/10.1002\/cpt.2894.","journal-title":"Clin Pharmacol Ther"},{"issue":"3","key":"1415_CR22","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1038\/clpt.2010.320","volume":"89","author":"MV Relling","year":"2011","unstructured":"Relling MV, Gardner EE, Sandborn WJ, Schmiegelow K, Pui CH, Yee SW, et al. Clinical Pharmacogenetics Implementation Consortium guidelines for thiopurine methyltransferase genotype and thiopurine dosing. Clin Pharmacol Ther. 2011;89(3):387\u201391. https:\/\/doi.org\/10.1038\/clpt.2010.320.","journal-title":"Clin Pharmacol Ther"},{"key":"1415_CR23","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.70209","author":"M Maillard","year":"2026","unstructured":"Maillard M, Schwab M, Whirl-Carrillo M, Moyer AM, Suarez-Kurtz G, Pui CH, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for Thiopurine Dosing Based on TPMT and NUDT15 Genotypes: 2025 Update. Clin Pharmacol Ther. 2026. https:\/\/doi.org\/10.1002\/cpt.70209.","journal-title":"Clin Pharmacol Ther"},{"issue":"9","key":"1415_CR24","doi-asserted-by":"publisher","first-page":"967","DOI":"10.1111\/apt.13796","volume":"44","author":"X Zhu","year":"2016","unstructured":"Zhu X, Wang XD, Chao K, Zhi M, Zheng H, Ruan HL, et al. NUDT15 polymorphisms are better than thiopurine S-methyltransferase as predictor of risk for thiopurine-induced leukopenia in Chinese patients with Crohn\u2019s disease. Aliment Pharmacol Ther. 2016;44(9):967\u201375. https:\/\/doi.org\/10.1111\/apt.13796.","journal-title":"Aliment Pharmacol Ther"},{"issue":"11","key":"1415_CR25","doi-asserted-by":"publisher","first-page":"1235","DOI":"10.1200\/jco.2014.59.4671","volume":"33","author":"JJ Yang","year":"2015","unstructured":"Yang JJ, Landier W, Yang W, Liu C, Hageman L, Cheng C, et al. Inherited NUDT15 variant is a genetic determinant of mercaptopurine intolerance in children with acute lymphoblastic leukemia. J Clin Oncol. 2015;33(11):1235\u201342. https:\/\/doi.org\/10.1200\/jco.2014.59.4671.","journal-title":"J Clin Oncol"},{"issue":"10","key":"1415_CR26","doi-asserted-by":"publisher","first-page":"1209","DOI":"10.1182\/blood-2017-05-782383","volume":"130","author":"T Moriyama","year":"2017","unstructured":"Moriyama T, Yang YL, Nishii R, Ariffin H, Liu C, Lin TN, et al. Novel variants in NUDT15 and thiopurine intolerance in children with acute lymphoblastic leukemia from diverse ancestry. Blood. 2017;130(10):1209\u201312. https:\/\/doi.org\/10.1182\/blood-2017-05-782383.","journal-title":"Blood"},{"issue":"9","key":"1415_CR27","doi-asserted-by":"publisher","first-page":"2145","DOI":"10.1038\/s41436-019-0448-7","volume":"21","author":"E Schaeffeler","year":"2019","unstructured":"Schaeffeler E, Jaeger SU, Klumpp V, Yang JJ, Igel S, Hinze L, et al. Impact of NUDT15 genetics on severe thiopurine-related hematotoxicity in patients with European ancestry. Genet Med. 2019;21(9):2145\u201350. https:\/\/doi.org\/10.1038\/s41436-019-0448-7.","journal-title":"Genet Med"},{"issue":"18","key":"1415_CR28","doi-asserted-by":"publisher","first-page":"5501","DOI":"10.1158\/0008-5472.Can-16-0584","volume":"76","author":"NC Valerie","year":"2016","unstructured":"Valerie NC, Hagenkort A, Page BD, Masuyer G, Rehling D, Carter M, et al. NUDT15 Hydrolyzes 6-Thio-DeoxyGTP to Mediate the Anticancer Efficacy of 6-Thioguanine. Cancer Res. 2016;76(18):5501\u201311. https:\/\/doi.org\/10.1158\/0008-5472.Can-16-0584.","journal-title":"Cancer Res"},{"issue":"6","key":"1415_CR29","doi-asserted-by":"publisher","first-page":"536","DOI":"10.1038\/tpj.2015.75","volume":"16","author":"DC Liang","year":"2016","unstructured":"Liang DC, Yang CP, Liu HC, Jaing TH, Chen SH, Hung IJ, et al. NUDT15 gene polymorphism related to mercaptopurine intolerance in Taiwan Chinese children with acute lymphoblastic leukemia. Pharmacogenomics J. 2016;16(6):536\u20139. https:\/\/doi.org\/10.1038\/tpj.2015.75.","journal-title":"Pharmacogenomics J"},{"issue":"2","key":"1415_CR30","doi-asserted-by":"publisher","first-page":"100183","DOI":"10.1016\/j.xhgg.2023.100183","volume":"4","author":"ML Nguyen","year":"2023","unstructured":"Nguyen ML, Hoang AV, Duong BT, Phung NTN. The influence of NUDT15 variants on 6-mercaptopurine-induced neutropenia in Vietnamese pediatric acute lymphoblastic leukemia. HGG Adv. 2023;4(2):100183. https:\/\/doi.org\/10.1016\/j.xhgg.2023.100183.","journal-title":"HGG Adv"},{"issue":"22","key":"1415_CR31","doi-asserted-by":"publisher","first-page":"10521","DOI":"10.1111\/jcmm.16981","volume":"25","author":"S Somazu","year":"2021","unstructured":"Somazu S, Tanaka Y, Tamai M, Watanabe A, Kagami K, Abe M, et al. NUDT15 polymorphism and NT5C2 and PRPS1 mutations influence thiopurine sensitivity in acute lymphoblastic leukaemia cells. J Cell Mol Med. 2021;25(22):10521\u201333. https:\/\/doi.org\/10.1111\/jcmm.16981.","journal-title":"J Cell Mol Med"},{"issue":"3","key":"1415_CR32","doi-asserted-by":"publisher","first-page":"872","DOI":"10.4143\/crt.2017.283","volume":"50","author":"ES Yi","year":"2018","unstructured":"Yi ES, Choi YB, Choi R, Lee NH, Lee JW, Yoo KH, et al. NUDT15 Variants Cause Hematopoietic Toxicity with Low 6-TGN Levels in Children with Acute Lymphoblastic Leukemia. Cancer Res Treat. 2018;50(3):872\u201382. https:\/\/doi.org\/10.4143\/crt.2017.283.","journal-title":"Cancer Res Treat"},{"issue":"22","key":"1415_CR33","doi-asserted-by":"publisher","first-page":"2466","DOI":"10.1182\/blood-2017-11-815506","volume":"131","author":"R Nishii","year":"2018","unstructured":"Nishii R, Moriyama T, Janke LJ, Yang W, Suiter CC, Lin TN, et al. Preclinical evaluation of NUDT15-guided thiopurine therapy and its effects on toxicity and antileukemic efficacy. Blood. 2018;131(22):2466\u201374. https:\/\/doi.org\/10.1182\/blood-2017-11-815506.","journal-title":"Blood"},{"issue":"5","key":"1415_CR34","doi-asserted-by":"publisher","first-page":"1095","DOI":"10.1002\/cpt.1304","volume":"105","author":"MV Relling","year":"2019","unstructured":"Relling MV, Schwab M, Whirl-Carrillo M, Suarez-Kurtz G, Pui CH, Stein CM, et al. Clinical Pharmacogenetics Implementation Consortium Guideline for Thiopurine Dosing Based on TPMT and NUDT15 Genotypes: 2018 Update. Clin Pharmacol Ther. 2019;105(5):1095\u2013105. https:\/\/doi.org\/10.1002\/cpt.1304.","journal-title":"Clin Pharmacol Ther"},{"issue":"7","key":"1415_CR35","doi-asserted-by":"publisher","first-page":"e293","DOI":"10.3324\/haematol.2018.187658","volume":"103","author":"Y Zhu","year":"2018","unstructured":"Zhu Y, Yin D, Su Y, Xia X, Moriyama T, Nishii R, et al. Combination of common and novel rare NUDT15 variants improves predictive sensitivity of thiopurine-induced leukopenia in children with acute lymphoblastic leukemia. Haematologica. 2018;103(7):e293\u20135. https:\/\/doi.org\/10.3324\/haematol.2018.187658.","journal-title":"Haematologica"},{"issue":"10","key":"1415_CR36","doi-asserted-by":"publisher","first-page":"5394","DOI":"10.1073\/pnas.1915680117","volume":"117","author":"CC Suiter","year":"2020","unstructured":"Suiter CC, Moriyama T, Matreyek KA, Yang W, Scaletti ER, Nishii R, et al. Massively parallel variant characterization identifies NUDT15 alleles associated with thiopurine toxicity. Proc Natl Acad Sci U S A. 2020;117(10):5394\u2013401. https:\/\/doi.org\/10.1073\/pnas.1915680117.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"3","key":"1415_CR37","doi-asserted-by":"publisher","first-page":"724","DOI":"10.1002\/cpt.3501","volume":"117","author":"M Maillard","year":"2025","unstructured":"Maillard M, Nguyen JQ, Yang W, Hoshitsuki K, Relling MV, Caudle KE, et al. Clinical Actionability of the NUDT15 *4 (p.R139H) Allele and Its Association With Hispanic Ethnicity. Clin Pharmacol Ther. 2025;117(3):724\u201331. https:\/\/doi.org\/10.1002\/cpt.3501.","journal-title":"Clin Pharmacol Ther"},{"issue":"5","key":"1415_CR38","doi-asserted-by":"publisher","first-page":"702","DOI":"10.1093\/jnci\/djae004","volume":"116","author":"M Maillard","year":"2024","unstructured":"Maillard M, Nishii R, Yang W, Hoshitsuki K, Chepyala D, Lee SHR, et al. Additive effects of TPMT and NUDT15 on thiopurine toxicity in children with acute lymphoblastic leukemia across multiethnic populations. J Natl Cancer Inst. 2024;116(5):702\u201310. https:\/\/doi.org\/10.1093\/jnci\/djae004.","journal-title":"J Natl Cancer Inst"},{"issue":"3","key":"1415_CR39","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1097\/00008571-200403000-00006","volume":"14","author":"AM Marinaki","year":"2004","unstructured":"Marinaki AM, Ansari A, Duley JA, Arenas M, Sumi S, Lewis CM, et al. Adverse drug reactions to azathioprine therapy are associated with polymorphism in the gene encoding inosine triphosphate pyrophosphatase (ITPase). Pharmacogenetics. 2004;14(3):181\u20137. https:\/\/doi.org\/10.1097\/00008571-200403000-00006.","journal-title":"Pharmacogenetics"},{"issue":"2","key":"1415_CR40","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1016\/j.mrrev.2013.08.001","volume":"753","author":"PD Simone","year":"2013","unstructured":"Simone PD, Pavlov YI, Borgstahl GEO. ITPA (inosine triphosphate pyrophosphatase): from surveillance of nucleotide pools to human disease and pharmacogenetics. Mutat Res. 2013;753(2):131\u201346. https:\/\/doi.org\/10.1016\/j.mrrev.2013.08.001.","journal-title":"Mutat Res"},{"issue":"1","key":"1415_CR41","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1186\/s12929-016-0291-y","volume":"23","author":"NE Burgis","year":"2016","unstructured":"Burgis NE. A disease spectrum for ITPA variation: advances in biochemical and clinical research. J Biomed Sci. 2016;23(1):73. https:\/\/doi.org\/10.1186\/s12929-016-0291-y.","journal-title":"J Biomed Sci"},{"issue":"2","key":"1415_CR42","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1111\/j.1365-2710.2011.01272.x","volume":"37","author":"WR Wan Rosalina","year":"2012","unstructured":"Wan Rosalina WR, Teh LK, Mohamad N, Nasir A, Yusoff R, Baba AA, et al. Polymorphism of ITPA 94C\u2009>\u2009A and risk of adverse effects among patients with acute lymphoblastic leukaemia treated with 6-mercaptopurine. J Clin Pharm Ther. 2012;37(2):237\u201341. https:\/\/doi.org\/10.1111\/j.1365-2710.2011.01272.x.","journal-title":"J Clin Pharm Ther"},{"key":"1415_CR43","doi-asserted-by":"publisher","first-page":"341","DOI":"10.2147\/tacg.S318912","volume":"14","author":"B Boonyawat","year":"2021","unstructured":"Boonyawat B, Monsereenusorn C, Photia A, Lertvivatpong N, Kaewchaivijit V, Jindatanmanusan P, et al. ITPA:c.94C\u2009>\u2009A and NUDT15:c.415C\u2009>\u2009T Polymorphisms and Their Relation to Mercaptopurine-Related Myelotoxicity in Childhood Leukemia in Thailand. Appl Clin Genet. 2021;14:341\u201351. https:\/\/doi.org\/10.2147\/tacg.S318912.","journal-title":"Appl Clin Genet"},{"key":"1415_CR44","doi-asserted-by":"publisher","first-page":"1159307","DOI":"10.3389\/fphar.2023.1159307","volume":"14","author":"AM Ali","year":"2023","unstructured":"Ali AM, Adam H, Hailu D, Engidawork E, Howe R, Abula T, et al. Genetic variants of genes involved in thiopurine metabolism pathway are associated with 6-mercaptopurine toxicity in pediatric acute lymphoblastic leukemia patients from Ethiopia. Front Pharmacol. 2023;14:1159307. https:\/\/doi.org\/10.3389\/fphar.2023.1159307.","journal-title":"Front Pharmacol"},{"issue":"7","key":"1415_CR45","doi-asserted-by":"publisher","first-page":"1585","DOI":"10.1111\/bcp.13943","volume":"85","author":"R Choi","year":"2019","unstructured":"Choi R, Sohn I, Kim MJ, Woo HI, Lee JW, Ma Y, et al. Pathway genes and metabolites in thiopurine therapy in Korean children with acute lymphoblastic leukaemia. Br J Clin Pharmacol. 2019;85(7):1585\u201397. https:\/\/doi.org\/10.1111\/bcp.13943.","journal-title":"Br J Clin Pharmacol"},{"issue":"10","key":"1415_CR46","doi-asserted-by":"publisher","first-page":"e109551","DOI":"10.1371\/journal.pone.0109551","volume":"9","author":"A Smid","year":"2014","unstructured":"Smid A, Karas-Kuzelicki N, Milek M, Jazbec J, Mlinaric-Rascan I. Association of ITPA genotype with event-free survival and relapse rates in children with acute lymphoblastic leukemia undergoing maintenance therapy. PLoS ONE. 2014;9(10):e109551. https:\/\/doi.org\/10.1371\/journal.pone.0109551.","journal-title":"PLoS ONE"},{"issue":"1","key":"1415_CR47","doi-asserted-by":"publisher","first-page":"516","DOI":"10.1186\/s12885-018-4398-2","volume":"18","author":"H Zhou","year":"2018","unstructured":"Zhou H, Li L, Yang P, Yang L, Zheng JE, Zhou Y, et al. Optimal predictor for 6-mercaptopurine intolerance in Chinese children with acute lymphoblastic leukemia: NUDT15, TPMT, or ITPA genetic variants? BMC Cancer. 2018;18(1):516. https:\/\/doi.org\/10.1186\/s12885-018-4398-2.","journal-title":"BMC Cancer"},{"key":"1415_CR48","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1016\/j.jpeds.2019.09.024","volume":"216","author":"M Wahlund","year":"2020","unstructured":"Wahlund M, Nilsson A, Kahlin AZ, Broliden K, Myrberg IH, Appell ML, et al. The Role of TPMT, ITPA, and NUDT15 Variants during Mercaptopurine Treatment of Swedish Pediatric Patients with Acute Lymphoblastic Leukemia. J Pediatr. 2020;216:150. 7.e1.","journal-title":"J Pediatr"},{"key":"1415_CR49","doi-asserted-by":"publisher","first-page":"100436","DOI":"10.1016\/j.dmpk.2021.100436","volume":"43","author":"K Khaeso","year":"2022","unstructured":"Khaeso K, Komvilaisak P, Chainansamit SO, Nakkam N, Suwannaying K, Kuwatjanakul P, et al. NUDT15 is a key genetic factor for prediction of hematotoxicity in pediatric patients who received a standard low dosage regimen of 6-mercaptopurine. Drug Metab Pharmacokinet. 2022;43:100436. https:\/\/doi.org\/10.1016\/j.dmpk.2021.100436.","journal-title":"Drug Metab Pharmacokinet"},{"key":"1415_CR50","doi-asserted-by":"publisher","unstructured":"Lee Y, Jang EJ, Yoon HY, Yee J, Gwak HS. Effect of ITPA polymorphism on adverse drug reactions of 6-mercaptopurine in pediatric patients with acute lymphoblastic leukemia: a systematic review and meta-analysis. Pharmaceuticals (Basel). 2022;15(4). https:\/\/doi.org\/10.3390\/ph15040416.","DOI":"10.3390\/ph15040416"},{"issue":"21","key":"1415_CR51","doi-asserted-by":"publisher","first-page":"4793","DOI":"10.1093\/hmg\/dds302","volume":"21","author":"G Stocco","year":"2012","unstructured":"Stocco G, Yang W, Crews KR, Thierfelder WE, Decorti G, Londero M, et al. PACSIN2 polymorphism influences TPMT activity and mercaptopurine-related gastrointestinal toxicity. Hum Mol Genet. 2012;21(21):4793\u2013804. https:\/\/doi.org\/10.1093\/hmg\/dds302.","journal-title":"Hum Mol Genet"},{"issue":"6","key":"1415_CR52","doi-asserted-by":"publisher","first-page":"925","DOI":"10.1038\/ajg.2014.89","volume":"109","author":"RL Roberts","year":"2014","unstructured":"Roberts RL, Wallace MC, Seinen ML, Krishnaprasad K, Chew A, Lawrance I, et al. PACSIN2 does not influence thiopurine-related toxicity in patients with inflammatory bowel disease. Am J Gastroenterol. 2014;109(6):925\u20137. https:\/\/doi.org\/10.1038\/ajg.2014.89.","journal-title":"Am J Gastroenterol"},{"issue":"4","key":"1415_CR53","doi-asserted-by":"publisher","first-page":"380","DOI":"10.1038\/tpj.2014.74","volume":"15","author":"Y Tanaka","year":"2015","unstructured":"Tanaka Y, Manabe A, Fukushima H, Suzuki R, Nakadate H, Kondoh K, et al. Multidrug resistance protein 4 (MRP4) polymorphisms impact the 6-mercaptopurine dose tolerance during maintenance therapy in Japanese childhood acute lymphoblastic leukemia. Pharmacogenomics J. 2015;15(4):380\u20134. https:\/\/doi.org\/10.1038\/tpj.2014.74.","journal-title":"Pharmacogenomics J"},{"issue":"5","key":"1415_CR54","doi-asserted-by":"publisher","first-page":"659","DOI":"10.1002\/humu.20694","volume":"29","author":"D Janke","year":"2008","unstructured":"Janke D, Mehralivand S, Strand D, G\u00f6dtel-Armbrust U, Habermeier A, Gradhand U, et al. 6-mercaptopurine and 9-(2-phosphonyl-methoxyethyl) adenine (PMEA) transport altered by two missense mutations in the drug transporter gene ABCC4. Hum Mutat. 2008;29(5):659\u201369. https:\/\/doi.org\/10.1002\/humu.20694.","journal-title":"Hum Mutat"},{"key":"1415_CR55","doi-asserted-by":"publisher","DOI":"10.1038\/s41431-025-01986-8","author":"MJH Coenen","year":"2025","unstructured":"Coenen MJH, Nijenhuis M, Soree B, de Boer-Veger NJ, Buunk AM, Guchelaar HJ, et al. Dutch Pharmacogenetics Working Group (DPWG) guideline for the gene-drug interaction between TPMT\/NUDT15 and thiopurines. Eur J Hum Genet. 2025. https:\/\/doi.org\/10.1038\/s41431-025-01986-8.","journal-title":"Eur J Hum Genet"},{"key":"1415_CR56","doi-asserted-by":"publisher","first-page":"115706","DOI":"10.1016\/j.biopha.2023.115706","volume":"168","author":"X D\u00edaz-Villamar\u00edn","year":"2023","unstructured":"D\u00edaz-Villamar\u00edn X, Fern\u00e1ndez-Var\u00f3n E, Rojas Romero MC, Callejas-Rubio JL, Cabeza-Barrera J, Rodr\u00edguez-Nogales A, et al. Azathioprine dose tailoring based on pharmacogenetic information: Insights of clinical implementation. Biomed Pharmacother. 2023;168:115706. https:\/\/doi.org\/10.1016\/j.biopha.2023.115706.","journal-title":"Biomed Pharmacother"},{"issue":"3","key":"1415_CR57","doi-asserted-by":"publisher","first-page":"835","DOI":"10.1053\/j.gastro.2017.07.031","volume":"153","author":"N Vande Casteele","year":"2017","unstructured":"Vande Casteele N, Herfarth H, Katz J, Falck-Ytter Y, Singh S. American Gastroenterological Association Institute Technical Review on the Role of Therapeutic Drug Monitoring in the Management of Inflammatory Bowel Diseases. Gastroenterology. 2017;153(3):835\u2013e576. https:\/\/doi.org\/10.1053\/j.gastro.2017.07.031.","journal-title":"Gastroenterology"},{"issue":"3","key":"1415_CR58","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1080\/17512433.2025.2465426","volume":"18","author":"LN Toksvang","year":"2025","unstructured":"Toksvang LN, Brigitha LJ, van der Sluis IM, Brivio E, Raja R, Pontoppidan P, et al. Therapeutic drug monitoring in acute lymphoblastic leukemia-a deep dive into pharmacokinetics, -dynamics, and -genetics of antileukemic drugs. Expert Rev Clin Pharmacol. 2025;18(3):131\u201349. https:\/\/doi.org\/10.1080\/17512433.2025.2465426.","journal-title":"Expert Rev Clin Pharmacol"},{"key":"1415_CR59","doi-asserted-by":"publisher","first-page":"941182","DOI":"10.3389\/fphar.2022.941182","volume":"13","author":"HL Guo","year":"2022","unstructured":"Guo HL, Zhao YT, Wang WJ, Dong N, Hu YH, Zhang YY, et al. Optimizing thiopurine therapy in children with acute lymphoblastic leukemia: A promising MINT sequencing strategy and therapeutic DNA-TG monitoring. Front Pharmacol. 2022;13:941182. https:\/\/doi.org\/10.3389\/fphar.2022.941182.","journal-title":"Front Pharmacol"},{"issue":"1","key":"1415_CR60","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1038\/clpt.1987.4","volume":"41","author":"L Lennard","year":"1987","unstructured":"Lennard L, Van Loon JA, Lilleyman JS, Weinshilboum RM. Thiopurine pharmacogenetics in leukemia: correlation of erythrocyte thiopurine methyltransferase activity and 6-thioguanine nucleotide concentrations. Clin Pharmacol Ther. 1987;41(1):18\u201325. https:\/\/doi.org\/10.1038\/clpt.1987.4.","journal-title":"Clin Pharmacol Ther"},{"key":"1415_CR61","doi-asserted-by":"publisher","unstructured":"Adam de Beaumais T, Medard Y, Amblard O, Goldwirt L, Simonin M, Martinez Vinson C, et al. Improved HPLC quantification of 6-mercaptopurine metabolites in red blood cells: monitoring data and literature analysis. Int J Mol Sci. 2022;23(19). https:\/\/doi.org\/10.3390\/ijms231911885.","DOI":"10.3390\/ijms231911885"},{"issue":"3","key":"1415_CR62","doi-asserted-by":"publisher","first-page":"e13870","DOI":"10.1016\/j.heliyon.2023.e13870","volume":"9","author":"H Yu","year":"2023","unstructured":"Yu H, Li D, Xiang D, Li X, Liu L, Liu D, et al. Development and validation of a novel HPLC-UV method for simultaneous determination of azathioprine metabolites in human red blood cells. Heliyon. 2023;9(3):e13870. https:\/\/doi.org\/10.1016\/j.heliyon.2023.e13870.","journal-title":"Heliyon"},{"issue":"6","key":"1415_CR63","doi-asserted-by":"publisher","first-page":"1236","DOI":"10.1002\/cpt.2730","volume":"112","author":"X Zhu","year":"2022","unstructured":"Zhu X, Chao K, Yang T, Wang XD, Guan S, Tang J, et al. DNA-Thioguanine Nucleotides as a Marker for Thiopurine Induced Late Leukopenia after Dose Optimizing by NUDT15 C415T in Chinese Patients with IBD. Clin Pharmacol Ther. 2022;112(6):1236\u201342. https:\/\/doi.org\/10.1002\/cpt.2730.","journal-title":"Clin Pharmacol Ther"},{"issue":"11","key":"1415_CR64","doi-asserted-by":"publisher","first-page":"999","DOI":"10.1007\/s00535-021-01820-0","volume":"56","author":"T Toyonaga","year":"2021","unstructured":"Toyonaga T, Kobayashi T, Kuronuma S, Ueno A, Kiyohara H, Okabayashi S, et al. Increased DNA-incorporated thiopurine metabolite as a possible mechanism for leukocytopenia through cell apoptosis in inflammatory bowel disease patients with NUDT15 mutation. J Gastroenterol. 2021;56(11):999\u20131007. https:\/\/doi.org\/10.1007\/s00535-021-01820-0.","journal-title":"J Gastroenterol"},{"issue":"1","key":"1415_CR65","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1007\/s00280-020-04219-5","volume":"88","author":"RH Larsen","year":"2021","unstructured":"Larsen RH, Hjalgrim LL, Degn M, Nersting J, Als-Nielsen B, Grell K, et al. Dynamics of leucocyte DNA thioguanine nucleotide levels during maintenance therapy of childhood acute lymphoblastic leukemia. Cancer Chemother Pharmacol. 2021;88(1):53\u201360. https:\/\/doi.org\/10.1007\/s00280-020-04219-5.","journal-title":"Cancer Chemother Pharmacol"},{"issue":"2","key":"1415_CR66","doi-asserted-by":"publisher","first-page":"145","DOI":"10.3343\/alm.2021.41.2.145","volume":"41","author":"R Choi","year":"2021","unstructured":"Choi R, Chun MR, Park J, Lee JW, Ju HY, Cho HW, et al. Quantification of Thioguanine in DNA Using Liquid Chromatography-Tandem Mass Spectrometry for Routine Thiopurine Drug Monitoring in Patients With Pediatric Acute Lymphoblastic Leukemia. Ann Lab Med. 2021;41(2):145\u201354. https:\/\/doi.org\/10.3343\/alm.2021.41.2.145.","journal-title":"Ann Lab Med"},{"issue":"2","key":"1415_CR67","doi-asserted-by":"publisher","first-page":"612","DOI":"10.1093\/ibd\/izae234","volume":"31","author":"AB Bayoumy","year":"2025","unstructured":"Bayoumy AB, Derijks LJJ, de Boer NKH. DNA-Thioguanine (DNA-TG) Is a Promising Novel Method to Predict Adverse Events to Thiopurine in Inflammatory Bowel Disease. Inflamm Bowel Dis. 2025;31(2):612\u20133. https:\/\/doi.org\/10.1093\/ibd\/izae234.","journal-title":"Inflamm Bowel Dis"},{"issue":"8","key":"1415_CR68","doi-asserted-by":"publisher","first-page":"1089","DOI":"10.1007\/s40262-024-01393-0","volume":"63","author":"AB Bayoumy","year":"2024","unstructured":"Bayoumy AB, Ansari AR, Mulder CJJ, Schmiegelow K, Florin T, De Boer NKH. Innovating Thiopurine Therapeutic Drug Monitoring: A Systematic Review and Meta-Analysis on DNA-Thioguanine Nucleotides (DNA-TG) as an Inclusive Biomarker in Thiopurine Therapy. Clin Pharmacokinet. 2024;63(8):1089\u2013109. https:\/\/doi.org\/10.1007\/s40262-024-01393-0.","journal-title":"Clin Pharmacokinet"},{"issue":"4","key":"1415_CR69","doi-asserted-by":"publisher","first-page":"515","DOI":"10.1016\/s1470-2045(17)30154-7","volume":"18","author":"SN Nielsen","year":"2017","unstructured":"Nielsen SN, Grell K, Nersting J, Abrahamsson J, Lund B, Kanerva J, et al. 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. Lancet Oncol. 2017;18(4):515\u201324. https:\/\/doi.org\/10.1016\/s1470-2045(17)30154-7.","journal-title":"Lancet Oncol"},{"issue":"1","key":"1415_CR70","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1038\/s41375-021-01182-9","volume":"36","author":"LN Toksvang","year":"2022","unstructured":"Toksvang LN, Grell K, Nersting J, Degn M, Nielsen SN, Abrahamsson J, et al. DNA-thioguanine concentration and relapse risk in children and young adults with acute lymphoblastic leukemia: an IPD meta-analysis. Leukemia. 2022;36(1):33\u201341. https:\/\/doi.org\/10.1038\/s41375-021-01182-9.","journal-title":"Leukemia"},{"issue":"6","key":"1415_CR71","doi-asserted-by":"publisher","first-page":"1114","DOI":"10.1002\/pbc.24913","volume":"61","author":"J Brackett","year":"2014","unstructured":"Brackett J, Schafer ES, Leung DH, Bernhardt MB. Use of allopurinol in children with acute lymphoblastic leukemia to reduce skewed thiopurine metabolism. Pediatr Blood Cancer. 2014;61(6):1114\u20137. https:\/\/doi.org\/10.1002\/pbc.24913.","journal-title":"Pediatr Blood Cancer"},{"issue":"4","key":"1415_CR72","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1111\/j.1365-2125.2010.03867.x","volume":"71","author":"T Adam de Beaumais","year":"2011","unstructured":"Adam de Beaumais T, Fakhoury M, Medard Y, Azougagh S, Zhang D, Yakouben K, et al. Determinants of mercaptopurine toxicity in paediatric acute lymphoblastic leukemia maintenance therapy. Br J Clin Pharmacol. 2011;71(4):575\u201384. https:\/\/doi.org\/10.1111\/j.1365-2125.2010.03867.x.","journal-title":"Br J Clin Pharmacol"},{"issue":"11","key":"1415_CR73","doi-asserted-by":"publisher","first-page":"2824","DOI":"10.3324\/haematol.2020.278166","volume":"106","author":"RH Larsen","year":"2021","unstructured":"Larsen RH, Utke Rank C, Grell K, N\u00f8rgaard M\u00f8ller L, Malthe Overgaard U, Kampmann P, et al. Increments in DNA-thioguanine level during thiopurine-enhanced maintenance therapy of acute lymphoblastic leukemia. Haematologica. 2021;106(11):2824\u201333. https:\/\/doi.org\/10.3324\/haematol.2020.278166.","journal-title":"Haematologica"},{"issue":"2","key":"1415_CR74","doi-asserted-by":"publisher","first-page":"555","DOI":"10.1038\/s41375-021-01420-0","volume":"36","author":"LN Toksvang","year":"2022","unstructured":"Toksvang LN, Grell K, Nielsen SN, Nersting J, Murdy D, Moorman AV, et al. DNA-TG and risk of sinusoidal obstruction syndrome in childhood acute lymphoblastic leukemia. Leukemia. 2022;36(2):555\u20137. https:\/\/doi.org\/10.1038\/s41375-021-01420-0.","journal-title":"Leukemia"},{"issue":"9","key":"1415_CR75","doi-asserted-by":"publisher","first-page":"2650","DOI":"10.1038\/s41375-021-01203-7","volume":"35","author":"M Stanulla","year":"2021","unstructured":"Stanulla M, Schaeffeler E, M\u00f6ricke A, Buchmann S, Zimmermann M, Igel S, et al. Hepatic sinusoidal obstruction syndrome and short-term application of 6-thioguanine in pediatric acute lymphoblastic leukemia. Leukemia. 2021;35(9):2650\u20137. https:\/\/doi.org\/10.1038\/s41375-021-01203-7.","journal-title":"Leukemia"},{"issue":"1","key":"1415_CR76","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1186\/s12885-022-09522-3","volume":"22","author":"LN Toksvang","year":"2022","unstructured":"Toksvang LN, Als-Nielsen B, Bacon C, Bertasiute R, Duarte X, Escherich G, et al. Thiopurine Enhanced ALL Maintenance (TEAM): study protocol for a randomized study to evaluate the improvement in disease-free survival by adding very low dose 6-thioguanine to 6-mercaptopurine\/methotrexate-based maintenance therapy in pediatric and adult patients (0\u201345 years) with newly diagnosed B-cell precursor or T-cell acute lymphoblastic leukemia treated according to the intermediate risk-high group of the ALLTogether1 protocol. BMC Cancer. 2022;22(1):483. https:\/\/doi.org\/10.1186\/s12885-022-09522-3.","journal-title":"BMC Cancer"},{"issue":"6","key":"1415_CR77","doi-asserted-by":"publisher","first-page":"810","DOI":"10.1038\/clpt.1983.254","volume":"34","author":"S Zimm","year":"1983","unstructured":"Zimm S, Collins JM, O\u2019Neill D, Chabner BA, Poplack DG. Inhibition of first-pass metabolism in cancer chemotherapy: interaction of 6-mercaptopurine and allopurinol. Clin Pharmacol Ther. 1983;34(6):810\u20137. https:\/\/doi.org\/10.1038\/clpt.1983.254.","journal-title":"Clin Pharmacol Ther"},{"issue":"6 Suppl","key":"1415_CR78","doi-asserted-by":"publisher","first-page":"655","DOI":"10.1136\/ard.25.Suppl_6.655","volume":"25","author":"RW Rundles","year":"1966","unstructured":"Rundles RW. Effects of allopurinol on 6-mercaptopurine therapy in neoplastic diseases. Ann Rheum Dis. 1966;25(6 Suppl):655\u20136. https:\/\/doi.org\/10.1136\/ard.25.Suppl_6.655.","journal-title":"Ann Rheum Dis"},{"issue":"4900","key":"1415_CR79","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1126\/science.2649979","volume":"244","author":"GB Elion","year":"1989","unstructured":"Elion GB. The purine path to chemotherapy. Science. 1989;244(4900):41\u20137. https:\/\/doi.org\/10.1126\/science.2649979.","journal-title":"Science"},{"issue":"6","key":"1415_CR80","first-page":"1283","volume":"32","author":"JJ Coffey","year":"1972","unstructured":"Coffey JJ, White CA, Lesk AB, Rogers WI, Serpick AA. Effect of allopurinol on the pharmacokinetics of 6-mercaptopurine (NSC 755) in cancer patients. Cancer Res. 1972;32(6):1283\u20139.","journal-title":"Cancer Res"},{"issue":"11","key":"1415_CR81","doi-asserted-by":"publisher","first-page":"1143","DOI":"10.1001\/jama.1975.03240230017012","volume":"231","author":"GP Rodnan","year":"1975","unstructured":"Rodnan GP, Robin JA, Tolchin SF, Elion GB. Allopurinol and gouty hyperuricemia. Efficacy of a single daily dose. JAMA. 1975;231(11):1143\u20137.","journal-title":"JAMA"},{"issue":"2","key":"1415_CR82","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1097\/mib.0000000000000197","volume":"21","author":"J Amin","year":"2015","unstructured":"Amin J, Huang B, Yoon J, Shih DQ. Update 2014: advances to optimize 6-mercaptopurine and azathioprine to reduce toxicity and improve efficacy in the management of IBD. Inflamm Bowel Dis. 2015;21(2):445\u201352. https:\/\/doi.org\/10.1097\/mib.0000000000000197.","journal-title":"Inflamm Bowel Dis"},{"issue":"12","key":"1415_CR83","doi-asserted-by":"publisher","first-page":"1286","DOI":"10.1111\/apt.15743","volume":"51","author":"AJ Czaja","year":"2020","unstructured":"Czaja AJ. Review article: opportunities to improve and expand thiopurine therapy for autoimmune hepatitis. Aliment Pharmacol Ther. 2020;51(12):1286\u2013304. https:\/\/doi.org\/10.1111\/apt.15743.","journal-title":"Aliment Pharmacol Ther"},{"issue":"2","key":"1415_CR84","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1002\/phar.2067","volume":"38","author":"GC Wall","year":"2018","unstructured":"Wall GC, Muktar H, Effken C, Mahajan PB. Addition of Allopurinol for Altering Thiopurine Metabolism to Optimize Therapy in Patients with Inflammatory Bowel Disease. Pharmacotherapy. 2018;38(2):259\u201370. https:\/\/doi.org\/10.1002\/phar.2067.","journal-title":"Pharmacotherapy"},{"issue":"4","key":"1415_CR85","doi-asserted-by":"publisher","first-page":"539","DOI":"10.1016\/j.bcp.2013.06.002","volume":"86","author":"PA Blaker","year":"2013","unstructured":"Blaker PA, Arenas-Hernandez M, Smith MA, Shobowale-Bakre EA, Fairbanks L, Irving PM, et al. Mechanism of allopurinol induced TPMT inhibition. Biochem Pharmacol. 2013;86(4):539\u201347. https:\/\/doi.org\/10.1016\/j.bcp.2013.06.002.","journal-title":"Biochem Pharmacol"},{"key":"1415_CR86","doi-asserted-by":"publisher","first-page":"101332","DOI":"10.1016\/j.eclinm.2022.101332","volume":"45","author":"M Kiszka-Kanowitz","year":"2022","unstructured":"Kiszka-Kanowitz M, Theede K, Thomsen SB, Bjerrum JT, Brynskov J, Gottschalck IB, et al. Low-dose azathioprine and allopurinol versus azathioprine monotherapy in patients with ulcerative colitis (AAUC): An investigator-initiated, open, multicenter, parallel-arm, randomised controlled trial. EClinicalMedicine. 2022;45:101332. https:\/\/doi.org\/10.1016\/j.eclinm.2022.101332.","journal-title":"EClinicalMedicine"},{"issue":"4","key":"1415_CR87","doi-asserted-by":"publisher","first-page":"504","DOI":"10.1111\/apt.17831","volume":"59","author":"A Vasudevan","year":"2024","unstructured":"Vasudevan A, Con D, De Cruz P, Sparrow MP, Friedman AB, Garg M, et al. Clinical trial: Combination allopurinol-thiopurine versus standard thiopurine in patients with IBD escalating to immunomodulators (the DECIDER study). Aliment Pharmacol Ther. 2024;59(4):504\u201314. https:\/\/doi.org\/10.1111\/apt.17831.","journal-title":"Aliment Pharmacol Ther"},{"issue":"4","key":"1415_CR88","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1111\/apt.15402","volume":"50","author":"JE Kreijne","year":"2019","unstructured":"Kreijne JE, de Veer RC, de Boer NK, Dijkstra G, West R, Moorsel SAW, et al. Real-life study of safety of thiopurine-allopurinol combination therapy in inflammatory bowel disease: myelotoxicity and hepatotoxicity rarely affect maintenance treatment. Aliment Pharmacol Ther. 2019;50(4):407\u201315. https:\/\/doi.org\/10.1111\/apt.15402.","journal-title":"Aliment Pharmacol Ther"},{"issue":"1","key":"1415_CR89","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1177\/2050640619868387","volume":"8","author":"SB Thomsen","year":"2020","unstructured":"Thomsen SB, Allin KH, Burisch J, Jensen CB, Hansen S, Gluud LL, et al. Outcome of concomitant treatment with thiopurines and allopurinol in patients with inflammatory bowel disease: A nationwide Danish cohort study. United Eur Gastroenterol J. 2020;8(1):68\u201376. https:\/\/doi.org\/10.1177\/2050640619868387.","journal-title":"United Eur Gastroenterol J"},{"issue":"11","key":"1415_CR90","doi-asserted-by":"publisher","first-page":"1076","DOI":"10.1111\/apt.15730","volume":"51","author":"VBC Biemans","year":"2020","unstructured":"Biemans VBC, Savelkoul E, Gabri\u00ebls RY, Simsek M, Dijkstra G, Pierik MJ, et al. A comparative analysis of tioguanine versus low-dose thiopurines combined with allopurinol in inflammatory bowel disease patients. Aliment Pharmacol Ther. 2020;51(11):1076\u201386. https:\/\/doi.org\/10.1111\/apt.15730.","journal-title":"Aliment Pharmacol Ther"},{"issue":"8","key":"1415_CR91","doi-asserted-by":"publisher","first-page":"1092","DOI":"10.1111\/apt.14571","volume":"47","author":"AB Friedman","year":"2018","unstructured":"Friedman AB, Brown SJ, Bampton P, Barclay ML, Chung A, Macrae FA, et al. Randomised clinical trial: efficacy, safety and dosage of adjunctive allopurinol in azathioprine\/mercaptopurine nonresponders (AAA Study). Aliment Pharmacol Ther. 2018;47(8):1092\u2013102. https:\/\/doi.org\/10.1111\/apt.14571.","journal-title":"Aliment Pharmacol Ther"},{"issue":"7","key":"1415_CR92","doi-asserted-by":"publisher","first-page":"682","DOI":"10.1016\/j.dld.2018.02.001","volume":"50","author":"A Vasudevan","year":"2018","unstructured":"Vasudevan A, Beswick L, Friedman AB, Moltzen A, Haridy J, Raghunath A, et al. Low-dose thiopurine with allopurinol co-therapy overcomes thiopurine intolerance and allows thiopurine continuation in inflammatory bowel disease. Dig Liver Dis. 2018;50(7):682\u20138. https:\/\/doi.org\/10.1016\/j.dld.2018.02.001.","journal-title":"Dig Liver Dis"},{"issue":"7","key":"1415_CR93","doi-asserted-by":"publisher","first-page":"1610","DOI":"10.3324\/haematol.2024.286882","volume":"110","author":"Y Mo","year":"2025","unstructured":"Mo Y, Zhang Q, Wang M, Chen J, Hu W, Chen C, et al. Results from patient-derived xenograft models support co-administration of allopurinol and 6-mercaptopurine to reduce hepatotoxicity and improve event-free survival in pediatric acute lymphoblastic leukemia. Haematologica. 2025;110(7):1610\u20135. https:\/\/doi.org\/10.3324\/haematol.2024.286882.","journal-title":"Haematologica"},{"issue":"9","key":"1415_CR94","doi-asserted-by":"publisher","first-page":"2846","DOI":"10.3324\/haematol.2023.284390","volume":"109","author":"J K\u00e4llstr\u00f6m","year":"2024","unstructured":"K\u00e4llstr\u00f6m J, Niinim\u00e4ki R, Fredlund J, Vogt H, Korhonen L, Castor A, et al. Effects of allopurinol on 6-mercaptopurine metabolism in unselected patients with pediatric acute lymphoblastic leukemia: a prospective phase II study. Haematologica. 2024;109(9):2846\u201353. https:\/\/doi.org\/10.3324\/haematol.2023.284390.","journal-title":"Haematologica"},{"issue":"10","key":"1415_CR95","doi-asserted-by":"publisher","first-page":"100154","DOI":"10.1016\/j.dmd.2025.100154","volume":"53","author":"Y Guan","year":"2025","unstructured":"Guan Y, Zhang X, Wang J, Xuan Q, Zhu X, Cao A, et al. 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. Drug Metab Dispos. 2025;53(10):100154. https:\/\/doi.org\/10.1016\/j.dmd.2025.100154.","journal-title":"Drug Metab Dispos"},{"key":"1415_CR96","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.70123","author":"Y Guan","year":"2025","unstructured":"Guan Y, Zhang X, Chan S, Su S, Xuan Q, Yang T, et al. Allopurinol Add-on 6-Mercaptopurine Strategy Improves Efficacy and Reduces Toxicity in Pediatric Patients With Acute Lymphoblastic Leukemia. Clin Pharmacol Ther. 2025. https:\/\/doi.org\/10.1002\/cpt.70123.","journal-title":"Clin Pharmacol Ther"},{"issue":"10","key":"1415_CR97","doi-asserted-by":"publisher","first-page":"2261","DOI":"10.3324\/haematol.2025.287774","volume":"110","author":"CG Van der Ham","year":"2025","unstructured":"Van der Ham CG, Van Leeuwen FN, Kuiper RP. Treatment-related mutagenic processes in acute lymphoblastic leukemia. Haematologica. 2025;110(10):2261\u201372. https:\/\/doi.org\/10.3324\/haematol.2025.287774.","journal-title":"Haematologica"},{"issue":"3","key":"1415_CR98","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1038\/nm.3119","volume":"19","author":"JC Aster","year":"2013","unstructured":"Aster JC, DeAngelo DJ. Resistance revealed in acute lymphoblastic leukemia. Nat Med. 2013;19(3):264\u20135. https:\/\/doi.org\/10.1038\/nm.3119.","journal-title":"Nat Med"},{"issue":"3","key":"1415_CR99","doi-asserted-by":"publisher","first-page":"368","DOI":"10.1038\/nm.3078","volume":"19","author":"G Tzoneva","year":"2013","unstructured":"Tzoneva G, Perez-Garcia A, Carpenter Z, Khiabanian H, Tosello V, Allegretta M, et al. Activating mutations in the NT5C2 nucleotidase gene drive chemotherapy resistance in relapsed ALL. Nat Med. 2013;19(3):368\u201371. https:\/\/doi.org\/10.1038\/nm.3078.","journal-title":"Nat Med"},{"issue":"7689","key":"1415_CR100","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1038\/nature25186","volume":"553","author":"G Tzoneva","year":"2018","unstructured":"Tzoneva G, Dieck CL, Oshima K, Ambesi-Impiombato A, S\u00e1nchez-Mart\u00edn M, Madubata CJ, et al. Clonal evolution mechanisms in NT5C2 mutant-relapsed acute lymphoblastic leukaemia. Nature. 2018;553(7689):511\u20134. https:\/\/doi.org\/10.1038\/nature25186.","journal-title":"Nature"},{"issue":"12","key":"1415_CR101","doi-asserted-by":"publisher","first-page":"2527","DOI":"10.1038\/s41375-018-0245-3","volume":"32","author":"M Tulstrup","year":"2018","unstructured":"Tulstrup M, Grosjean M, Nielsen SN, Grell K, Wolthers BO, Wegener PS, et al. NT5C2 germline variants alter thiopurine metabolism and are associated with acquired NT5C2 relapse mutations in childhood acute lymphoblastic leukaemia. Leukemia. 2018;32(12):2527\u201335. https:\/\/doi.org\/10.1038\/s41375-018-0245-3.","journal-title":"Leukemia"},{"issue":"6","key":"1415_CR102","doi-asserted-by":"publisher","first-page":"1538","DOI":"10.1002\/cpt.2095","volume":"109","author":"C Jiang","year":"2021","unstructured":"Jiang C, Yang W, Moriyama T, Liu C, Smith C, Yang W, et al. Effects of NT5C2 Germline Variants on 6-Mecaptopurine Metabolism in Children With Acute Lymphoblastic Leukemia. Clin Pharmacol Ther. 2021;109(6):1538\u201345. https:\/\/doi.org\/10.1002\/cpt.2095.","journal-title":"Clin Pharmacol Ther"},{"issue":"10","key":"1415_CR103","doi-asserted-by":"publisher","first-page":"1887","DOI":"10.1158\/1535-7163.Mct-18-1112","volume":"18","author":"T Moriyama","year":"2019","unstructured":"Moriyama T, Liu S, Li J, Meyer J, Zhao X, Yang W, et al. Mechanisms of NT5C2-Mediated Thiopurine Resistance in Acute Lymphoblastic Leukemia. Mol Cancer Ther. 2019;18(10):1887\u201395. https:\/\/doi.org\/10.1158\/1535-7163.Mct-18-1112.","journal-title":"Mol Cancer Ther"},{"issue":"4","key":"1415_CR104","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1124\/molpharm.122.000546","volume":"103","author":"TTT Nguyen","year":"2023","unstructured":"Nguyen TTT, Tanaka Y, Sanada M, Hosaka M, Tamai M, Kagami K, et al. CRISPR\/Cas9-Mediated Induction of Relapse-Specific NT5C2 and PRPS1 Mutations Confers Thiopurine Resistance as a Relapsed Lymphoid Leukemia Model. Mol Pharmacol. 2023;103(4):199\u2013210. https:\/\/doi.org\/10.1124\/molpharm.122.000546.","journal-title":"Mol Pharmacol"},{"issue":"1","key":"1415_CR105","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1016\/j.ccell.2018.06.003","volume":"34","author":"CL Dieck","year":"2018","unstructured":"Dieck CL, Tzoneva G, Forouhar F, Carpenter Z, Ambesi-Impiombato A, S\u00e1nchez-Mart\u00edn M, et al. Structure and Mechanisms of NT5C2 Mutations Driving Thiopurine Resistance in Relapsed Lymphoblastic Leukemia. Cancer Cell. 2018;34(1):136\u2013e476. https:\/\/doi.org\/10.1016\/j.ccell.2018.06.003.","journal-title":"Cancer Cell"},{"issue":"11","key":"1415_CR106","doi-asserted-by":"publisher","first-page":"2646","DOI":"10.1158\/2159-8290.Cd-22-0010","volume":"12","author":"C Reglero","year":"2022","unstructured":"Reglero C, Dieck CL, Zask A, Forouhar F, Laurent AP, Lin WW, et al. Pharmacologic Inhibition of NT5C2 Reverses Genetic and Nongenetic Drivers of 6-MP Resistance in Acute Lymphoblastic Leukemia. Cancer Discov. 2022;12(11):2646\u201365. https:\/\/doi.org\/10.1158\/2159-8290.Cd-22-0010.","journal-title":"Cancer Discov"},{"issue":"20","key":"1415_CR107","doi-asserted-by":"publisher","first-page":"3327","DOI":"10.1158\/0008-5472.Can-23-3804","volume":"84","author":"M Torres-Diz","year":"2024","unstructured":"Torres-Diz M, Reglero C, Falkenstein CD, Castro A, Hayer KE, Radens CM, et al. An Alternatively Spliced Gain-of-Function NT5C2 Isoform Contributes to Chemoresistance in Acute Lymphoblastic Leukemia. Cancer Res. 2024;84(20):3327\u201336. https:\/\/doi.org\/10.1158\/0008-5472.Can-23-3804.","journal-title":"Cancer Res"},{"issue":"6","key":"1415_CR108","doi-asserted-by":"publisher","first-page":"563","DOI":"10.1038\/nm.3840","volume":"21","author":"B Li","year":"2015","unstructured":"Li B, Li H, Bai Y, Kirschner-Schwabe R, Yang JJ, Chen Y, et al. Negative feedback-defective PRPS1 mutants drive thiopurine resistance in relapsed childhood ALL. Nat Med. 2015;21(6):563\u201371. https:\/\/doi.org\/10.1038\/nm.3840.","journal-title":"Nat Med"},{"issue":"5","key":"1415_CR109","doi-asserted-by":"publisher","first-page":"830","DOI":"10.3324\/haematol.2017.176362","volume":"103","author":"NA Evensen","year":"2018","unstructured":"Evensen NA, Madhusoodhan PP, Meyer J, Saliba J, Chowdhury A, Araten DJ, et al. MSH6 haploinsufficiency at relapse contributes to the development of thiopurine resistance in pediatric B-lymphoblastic leukemia. Haematologica. 2018;103(5):830\u20139. https:\/\/doi.org\/10.3324\/haematol.2017.176362.","journal-title":"Haematologica"},{"issue":"6778","key":"1415_CR110","doi-asserted-by":"publisher","first-page":"1143","DOI":"10.1126\/science.adv4257","volume":"390","author":"TA Nguyen","year":"2025","unstructured":"Nguyen TA, Lin JG, Marques AMC, Fottner M, Bauer LG, Reicher A, et al. A non-enzymatic role of Nudix hydrolase 5 in repressing purine de novo synthesis. Science. 2025;390(6778):1143\u201350. https:\/\/doi.org\/10.1126\/science.adv4257.","journal-title":"Science"},{"issue":"6778","key":"1415_CR111","doi-asserted-by":"publisher","first-page":"1134","DOI":"10.1126\/science.adx9717","volume":"390","author":"Z Wu","year":"2025","unstructured":"Wu Z, Nguyen PT, Sondhi V, Yao RW, Lu Z, Dai T, et al. NUDT5 regulates purine metabolism and thiopurine sensitivity by interacting with PPAT. Science. 2025;390(6778):1134\u201342. https:\/\/doi.org\/10.1126\/science.adx9717.","journal-title":"Science"},{"key":"1415_CR112","doi-asserted-by":"publisher","unstructured":"Maillard M, Nishii R, Vu HS, Bhattarai KR, Yang W, Li J, et al. The NUDIX hydrolase NUDT5 regulates thiopurine metabolism and cytotoxicity. J Clin Invest. 2025;135(14). https:\/\/doi.org\/10.1172\/jci190443.","DOI":"10.1172\/jci190443"}],"container-title":["Current Treatment Options in Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11864-026-01415-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s11864-026-01415-y","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11864-026-01415-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T06:59:32Z","timestamp":1791269972000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s11864-026-01415-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,6]]},"references-count":112,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,12]]}},"alternative-id":["1415"],"URL":"https:\/\/doi.org\/10.1007\/s11864-026-01415-y","relation":{},"ISSN":["1527-2729","1534-6277"],"issn-type":[{"value":"1527-2729","type":"print"},{"value":"1534-6277","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,6]]},"assertion":[{"value":"4 March 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 September 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 October 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This article does not contain any studies with human or animal subjects performed by any of the authors.","order":2,"name":"Ethics","label":"Human and Animal Rights and Informed Consent","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"No AI-assisted tools were used in the writing of this article. All content has been reviewed and revised by the authors, who take full responsibility for the accuracy and integrity of the final content.","order":3,"name":"Ethics","label":"Generative AI in Scientific Writing","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"49"}}