{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T05:04:33Z","timestamp":1790744673112,"version":"4.1.0"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Core-binding factor acute myeloid leukemia (CBF-AML) is defined by one of two founding fusions, but cooperating lesions may differ between fusion subtypes. We characterized the broader diagnostic co-mutational architecture of pediatric CBF-AML and examined its relationship with post-induction measurable residual disease (MRD) and outcome.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This retrospective analysis included 170 children with diagnostic whole-exome sequencing (WES) data (2019\u20132023), a subset of a reported 289-patient cohort. Candidate leukemia-associated variants were curated conservatively because matched normal samples were unavailable. Variant frequencies were compared between RUNX1::RUNX1T1 and CBFB::MYH11 AML with false-discovery-rate control. Associations with MRD were tested using Fisher\u2019s exact test. Primary feature-specific Cox models for event-free survival (EFS) were adjusted only for fusion subtype and induction regimen; sensitivity analyses additionally addressed age and presenting WBC count, MRD, and transplantation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In a limited selection audit, fusion-subtype and FLT3-ITD distributions were similar between WES-included and non-included patients, whereas clinical-source KIT positivity was more frequent in the WES subset. The analytic cohort included 138 RUNX1::RUNX1T1 and 32 CBFB::MYH11 cases; 137 received FLAG-IDA, and 33 received DAE induction. At least one curated candidate variant was present in 135 patients (79.4%), and 69 (40.6%) had alterations in two or more genes. Tyrosine-kinase signaling alterations occurred in 115 patients (67.6%). RAS-pathway alterations were enriched in CBFB::MYH11 AML (53.1% vs. 19.6%; P &amp;lt; 0.001, q=0.002), driven principally by NRAS (50.0% vs. 15.2%; P &amp;lt; 0.001, q &amp;lt; 0.001). Chromatin-modifier alterations were numerically enriched in RUNX1::RUNX1T1 AML (24.6% vs. 6.2%; P\u00a0=\u00a00.028) but did not remain significant after multiplicity correction (q=0.114). After false-discovery-rate correction, no tested genomic feature was associated with MFC-MRD or molecular MRD positivity after the second induction. With a median follow-up of 33.2 months, 3-year EFS and overall survival were 84.2% and 89.8%, respectively. No baseline genomic feature showed a significant association with EFS in either the primary or expanded baseline-covariate models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Among WES-profiled patients, pediatric CBF-AML showed fusion-specific co-mutational architecture, especially RAS-pathway enrichment in CBFB::MYH11 AML. In this WES-defined cohort, baseline genomic features were not established as response or outcome predictors. These findings are descriptive and hypothesis-generating; they do not support treatment-specific causal inference.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2026.1897872","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T04:49:46Z","timestamp":1790743786000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Fusion-specific co-mutational architecture and treatment-response associations in pediatric core-binding factor acute myeloid leukemia: a multicenter exome-profiled cohort"],"prefix":"10.3389","volume":"16","author":[{"given":"Mei","family":"Li","sequence":"first","affiliation":[{"name":"Department of Pediatric Hematology, Fujian Institute of Hematology, Fujian Provincial Key Laboratory on Hematology, Fujian Medical University Union Hospital","place":["Fuzhou, 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