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However, the functional impact of dysregulation of the epigenome and transcriptome in this context remains poorly understood. In this study, we combined ex vivo drug sensitivity profiling with transcriptomic and epigenomic analyses in diagnostic samples from 597 pediatric B\u2010cell precursor acute lymphoblastic leukemia (BCP\u2010ALL) patients. Ex vivo resistance to antimetabolites (e.g., cytarabine, thioguanine), glucocorticoids (e.g., dexamethasone, prednisolone), and doxorubicin was independently associated with reduced relapse\u2010free survival (P\u2009&lt;\u20090.05). Molecular profiling identified pretreatment DNA methylation and gene expression patterns distinguishing resistant from sensitive cases, revealing key drug resistance signatures. These included aberrant expression of genes related to heme metabolism (e.g.,\n                    <jats:italic>ATPV06A<\/jats:italic>\n                    ) and\n                    <jats:italic>KRAS<\/jats:italic>\n                    signaling (e.g.,\n                    <jats:italic>GS02<\/jats:italic>\n                    ). Notably, we also observed atypical expression of genes usually restricted to T cells and other immune cells (e.g.,\n                    <jats:italic>ITK<\/jats:italic>\n                    ) in resistant BCP\u2010ALL cells. Our findings demonstrate that ex vivo drug response patterns are predictive of clinical outcomes and reflect intrinsic molecular states associated with drug tolerance. This integrative multi\u2010omics approach highlights potential therapeutic targets and underscores the value of functional precision medicine in identifying treatment vulnerabilities in pediatric ALL.\n                  <\/jats:p>","DOI":"10.1002\/hem3.70176","type":"journal-article","created":{"date-parts":[[2025,7,28]],"date-time":"2025-07-28T09:21:53Z","timestamp":1753694513000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Ex vivo drug responses and molecular profiles of 597 pediatric acute lymphoblastic leukemia patients"],"prefix":"10.1002","volume":"9","author":[{"given":"Anna Pia","family":"Enblad","sequence":"first","affiliation":[{"name":"Department of Medical Sciences Uppsala University Uppsala Sweden"},{"name":"Science for Life Laboratory Uppsala University Uppsala Sweden"},{"name":"Department of Women's and Children's Health Uppsala University Uppsala 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