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Bulk RNA-seq analysis of bone marrow was realized to identify molecular subtypes in Mexican pediatric patients with B-ALL. High hyperdiploidy (27.3%) was the most frequent molecular subtype, followed by DUX4 (13.6%), TCF3::PBX1 (9.1%), ETV6::RUNX1 (9.1%), Ph-like (9.1%), ETV6::RUNX1-like (9.1%), PAX5alt (4.5%), Ph (4.5%), KMT2A (4.5%), and ZNF384 (4.5%), with one patient presenting both the PAX5alt and low hypodiploidy subtypes (4.5%). The genes TYK2, SEMA6A, FLT3, NRAS, SETD2, JAK2, NT5C2, RAG1, and SPATS2L harbor deleterious missense variants across different B-ALL molecular subtypes. The Ph-like subtype exhibited mutations in STAT2, ADGRF1, TCF3, BCR, JAK2, and NRAS with overexpression of the CRLF2 gene. The DUX4 subtype showed mutually exclusive missense variants in the PDGRFA gene. Here, we have demonstrated the importance of using RNA-seq to facilitate the differential diagnosis of B-ALL with successful detection of gene fusions and mutations. This will aid both patient risk stratification and precision medicine.<\/jats:p>","DOI":"10.3390\/ijms26147003","type":"journal-article","created":{"date-parts":[[2025,7,21]],"date-time":"2025-07-21T13:59:11Z","timestamp":1753106351000},"page":"7003","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Identification of Molecular Subtypes of B-Cell Acute Lymphoblastic Leukemia in Mexican Children by Whole-Transcriptome Analysis"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1030-5938","authenticated-orcid":false,"given":"Norberto","family":"S\u00e1nchez-Escobar","sequence":"first","affiliation":[{"name":"SECIHTI-Facultad de Medicina y Cirug\u00eda-Universidad Aut\u00f3noma \u201cBenito Ju\u00e1rez\u201d de Oaxaca, Mexico City 68020, Mexico"},{"name":"Unidad de Investigaci\u00f3n M\u00e9dica en Gen\u00e9tica Humana, Hospital de Pediatr\u00eda \u201cDr. Silvestre Frenk 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