{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T05:07:55Z","timestamp":1779944875710,"version":"3.53.1"},"reference-count":23,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","license":[{"start":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T00:00:00Z","timestamp":1769990400000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,7]]},"abstract":"\n Objective<\/jats:title>\n \n To characterize the allelic and diplotype variability of\n TPMT<\/jats:italic>\n and\n NUDT15<\/jats:italic>\n in pediatric patients with B-cell acute lymphoblastic leukemia from the central-southern region of Mexico.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Samples from 275 pediatric B-cell acute lymphoblastic leukemia patients were analyzed. Next-generation sequencing was used for\n TPMT<\/jats:italic>\n and\n NUDT15<\/jats:italic>\n genotyping. Alleles and diplotypes were assessed according to the Clinical Pharmacogenetics Implementation Consortium guidelines. Their geographic distribution was compared across Mexican states and global populations. In-silico analyses were conducted to assess the structural and functional impact of\n TPMT<\/jats:italic>\n variants not associated with star alleles.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n The wild-type *1 allele, associated with normal enzymatic activity, was predominant in both genes:\n TPMT<\/jats:italic>\n (94.15%) and\n NUDT15<\/jats:italic>\n (90.45%).\n TPMT<\/jats:italic>\n showed greater allelic diversity compared with previous studies in Mexican populations. Alleles conferring absent or indeterminate enzymatic activity in\n TPMT<\/jats:italic>\n were distributed across six diplotypes (11.62%), with *3A allele (4.73%) and *1\n \/<\/jats:italic>\n *3A diplotype (9.45%) being the most frequent. Additionally, two unclassified\n TPMT<\/jats:italic>\n variants, p.G126A and p.D137Y, were identified. For\n NUDT15<\/jats:italic>\n , three non-wild-type diplotypes were observed (19.09%), with the *2 allele (6.74%) and *1*\n \/<\/jats:italic>\n 2 diplotype (13.48%) being the most prevalent.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n Approximately 28% of patients carried\n TPMT<\/jats:italic>\n and\/or\n NUDT15<\/jats:italic>\n variants associated with non-wild-type enzymatic activity, increasing the risk of mercaptopurine-induced myelotoxicity. Preemptive genotyping is essential to reduce toxicity, optimize treatment, and advance precision medicine in this population. Additionally, the two\n TPMT<\/jats:italic>\n variants p.G126A and p.D137Y, currently not classified within Clinical Pharmacogenetics Implementation Consortium-defined star alleles, highlight the need for functional validation and potential clinical classification to improve pharmacogenetic interpretation in diverse populations.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1097\/fpc.0000000000000593","type":"journal-article","created":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T08:00:08Z","timestamp":1770105608000},"page":"143-150","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":0,"title":["Prevalence of TPMT and NUDT15 diplotypes in Mexican children with B-cell acute lymphoblastic leukemia"],"prefix":"10.1097","volume":"36","author":[{"given":"Joaquin","family":"Garcia-Solorio","sequence":"first","affiliation":[{"name":"Laboratorio de Diagn\u00f3stico Gen\u00f3mico, Instituto Nacional de Medicina Gen\u00f3mica (INMEGEN)"},{"name":"Escuela Nacional de Ciencias Biol\u00f3gicas (ENCB)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina","family":"Molina-Garay","sequence":"additional","affiliation":[{"name":"Laboratorio de Diagn\u00f3stico Gen\u00f3mico, Instituto Nacional de Medicina Gen\u00f3mica (INMEGEN)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V\u00edctor Jes\u00fas","family":"S\u00e1nchez-Mart\u00ednez","sequence":"additional","affiliation":[{"name":"Laboratorio de Diagn\u00f3stico Gen\u00f3mico, Instituto Nacional de Medicina Gen\u00f3mica (INMEGEN)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatriz Eugenia","family":"Villegas-Torres","sequence":"additional","affiliation":[{"name":"Laboratorio de Diagn\u00f3stico Gen\u00f3mico, Instituto Nacional de Medicina Gen\u00f3mica (INMEGEN)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irlanda","family":"Campos-Perez","sequence":"additional","affiliation":[{"name":"Departamento de Oncolog\u00eda, Instituto Nacional de Pediatr\u00eda (INP), Mexico City"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Jim\u00e9nez-Olivares","sequence":"additional","affiliation":[{"name":"Laboratorio de Diagn\u00f3stico Gen\u00f3mico, Instituto Nacional de Medicina Gen\u00f3mica (INMEGEN)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernanda","family":"Flores-Espino","sequence":"additional","affiliation":[{"name":"Laboratorio de Diagn\u00f3stico Gen\u00f3mico, Instituto Nacional de Medicina Gen\u00f3mica (INMEGEN)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Casique-Aguirre","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica de Oriente (CIBIOR), Instituto Mexicano del Seguro Social (IMSS), Puebla"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Carlos","family":"N\u00fa\u00f1ez-Enriquez","sequence":"additional","affiliation":[{"name":"Unidad de Investigaci\u00f3n M\u00e9dica en Epidemiolog\u00eda Cl\u00ednica, UMAE Hospital de Pediatr\u00eda, Centro M\u00e9dico Nacional (CMN) Siglo XXI, Instituto Mexicano del Seguro Social (IMSS)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janet","family":"Flores-Lujano","sequence":"additional","affiliation":[{"name":"Unidad de Investigaci\u00f3n M\u00e9dica en Epidemiolog\u00eda Cl\u00ednica, UMAE Hospital de Pediatr\u00eda, Centro M\u00e9dico Nacional (CMN) Siglo XXI, Instituto Mexicano del Seguro Social (IMSS)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minerva","family":"Mata-Rocha","sequence":"additional","affiliation":[{"name":"Unidad de Investigaci\u00f3n M\u00e9dica en Gen\u00e9tica Humana, Hospital de Pediatr\u00eda, CMN Siglo XXI, Instituto Mexicano del Seguro Social (IMSS)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Gabriel","family":"Pe\u00f1aloza-Gonzalez","sequence":"additional","affiliation":[{"name":"Servicio de Onco-Pediatr\u00eda, Hospital Ju\u00e1rez de M\u00e9xico, SSA; Mexico City"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor Hugo","family":"Olivares-Villalpando","sequence":"additional","affiliation":[{"name":"Servicio de Onco-Pediatr\u00eda, Hospital Ju\u00e1rez de M\u00e9xico, SSA; Mexico City"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ma Del Roc\u00edo","family":"Ba\u00f1os-Lara","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Oncol\u00f3gica, Una Nueva Esperanza A.C. Universidad Popular Aut\u00f3noma de Puebla, Puebla"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c1ngel","family":"Garc\u00eda-Soto","sequence":"additional","affiliation":[{"name":"Hospital General Centro M\u00e9dico La Raza, Instituto Mexicano del Seguro Social (IMSS), Mexico City, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9sar Alejandro","family":"Galv\u00e1n-D\u00edaz","sequence":"additional","affiliation":[{"name":"Departamento de Oncolog\u00eda, Instituto Nacional de Pediatr\u00eda (INP), Mexico City"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Olaya-Vargas","sequence":"additional","affiliation":[{"name":"Departamento de Oncolog\u00eda, Instituto Nacional de Pediatr\u00eda (INP), Mexico City"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moises","family":"Solano-Cardozo","sequence":"additional","affiliation":[{"name":"Hospital General Regional 01, Culiacan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel \u00c1ngel","family":"Garrido-Hern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Servicio de Oncohematolog\u00eda Pedi\u00e1trica, Hospital para el Ni\u00f1o Poblano, Secretar\u00eda de Salud (SS), Puebla"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nuria Citlalli","family":"Luna-Silva","sequence":"additional","affiliation":[{"name":"Servicio de Hemato-Oncolog\u00eda Pedi\u00e1trica, Hospital de la Ni\u00f1ez Oaxaque\u00f1a \u2018Dr. Guillermo Z\u00e1rate Mijangos\u2019, Secretaria de Salud y Servicios de Salud Oaxaca (SSO), Oaxaca"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lena Sarahi","family":"Cano-Cuapio","sequence":"additional","affiliation":[{"name":"Hospital Infantil de Tlaxcala, Servicio de Oncolog\u00eda Pedi\u00e1trica, Tlaxcala"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karol","family":"Carrillo-Sanchez","sequence":"additional","affiliation":[{"name":"Laboratorio de Diagn\u00f3stico Gen\u00f3mico, Instituto Nacional de Medicina Gen\u00f3mica (INMEGEN)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis Leonardo","family":"Flores-Lagunes","sequence":"additional","affiliation":[{"name":"Laboratorio de Diagn\u00f3stico Gen\u00f3mico, Instituto Nacional de Medicina Gen\u00f3mica (INMEGEN)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elvia Cristina","family":"Mendoza-Caamal","sequence":"additional","affiliation":[{"name":"Laboratorio de Diagn\u00f3stico Gen\u00f3mico, Instituto Nacional de Medicina Gen\u00f3mica (INMEGEN)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Gonz\u00e1lez-Osnaya","sequence":"additional","affiliation":[{"name":"Laboratorio de Diagn\u00f3stico Gen\u00f3mico, Instituto Nacional de Medicina Gen\u00f3mica (INMEGEN)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosana","family":"Pelayo-Camacho","sequence":"additional","affiliation":[{"name":"Laboratorio de Cit\u00f3mica del C\u00e1ncer Infantil, Centro de Investigaci\u00f3n Biom\u00e9dica de Oriente, Delegaci\u00f3n Puebla, Instituto Mexicano del Seguro Social, Puebla"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Manuel","family":"Mej\u00eda-Arangure","sequence":"additional","affiliation":[{"name":"Laboratorio de Gen\u00f3mica del C\u00e1ncer, Instituto Nacional de Medicina Gen\u00f3mica (INMEGEN)"},{"name":"Facultad de Medicina, Universidad Nacional Aut\u00f3noma de M\u00e9xico (UNAM), M\u00e9xico City, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun J","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, St. Jude Children\u2019s Research Hospital, Memphis, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Alaez-Verson","sequence":"additional","affiliation":[{"name":"Laboratorio de Diagn\u00f3stico Gen\u00f3mico, Instituto Nacional de Medicina Gen\u00f3mica (INMEGEN)"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2026,2,2]]},"reference":[{"key":"R1-20260528","doi-asserted-by":"crossref","first-page":"1072811","DOI":"10.3389\/fonc.2022.1072811","article-title":"Triple-hit explanation for the worse prognosis of pediatric acute lymphoblastic leukemia among Mexican and Hispanic children.","volume":"12","author":"Rivera-Luna","year":"2022","journal-title":"Front Oncol"},{"key":"R2-20260528","doi-asserted-by":"crossref","first-page":"1299355","DOI":"10.3389\/fonc.2023.1299355","article-title":"The genetic risk of acute lymphoblastic leukemia and its implications for children of Latin American origin.","volume":"13","author":"de 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