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Despite therapeutic advances, relapses remain common, and survival for high\u2010risk patients is below 60%. Unlike adult AML, pediatric AML displays distinct genetic mutations, including FLT3\u2010ITD, NPM1, KMT2A rearrangements, and core\u2010binding factors (CBF) fusions, as well as extensive epigenetic dysregulation. Aberrant DNA methylation, histone modifications, and altered non\u2010coding RNA expressions disrupt hematopoietic differentiation and activate oncogenic transcriptional networks. Recent advances\n                    <jats:italic>in silico<\/jats:italic>\n                    transcriptomic analysis have transformed the study of pediatric AML by integrating gene expression and epigenetic data to identify molecular drivers and regulatory networks. Computational RNA\u2010seq pipelines and pathway analyses have highlighted key epigenetic regulators, including DNMT3A, TET2, and HDACs, as potential therapeutic targets. Multi\u2010omics approaches combining transcriptomic, methylomic, and chromatin accessibility data are increasingly used to define biomarkers for diagnosis, prognosis, and therapeutic response. This review provides a comprehensive overview of the molecular and epigenetic landscape of pediatric AML, emphasizing the power of\n                    <jats:italic>in silico<\/jats:italic>\n                    transcriptome analysis to uncover disease mechanisms, refine patient stratification, and guide the development of precision\u2010based epigenetic therapies aimed at improving long\u2010term outcomes in children with AML.\n                  <\/jats:p>","DOI":"10.1111\/ejh.70230","type":"journal-article","created":{"date-parts":[[2026,5,23]],"date-time":"2026-05-23T01:45:53Z","timestamp":1779500753000},"page":"767-786","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Epigenetics and In Silico Transcriptome Analysis of Pediatric Acute Myeloid Leukemia"],"prefix":"10.1111","volume":"117","author":[{"given":"Akram N.","family":"Salah","sequence":"first","affiliation":[{"name":"Microbiology and Immunology 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