{ "abstract": "Introduction: 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.\n\nMethods: This retrospective analysis included 170 children with diagnostic whole-exome sequencing (WES) data (2019–2023), 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’s 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.\n\nResults: 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 < 0.001, q=0.002), driven principally by NRAS (50.0% vs. 15.2%; P < 0.001, q < 0.001). Chromatin-modifier alterations were numerically enriched in RUNX1::RUNX1T1 AML (24.6% vs. 6.2%; P = 0.028) 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.\n\nConclusions: 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.", "abstract_shown": true, "affiliations": [ "Department of Pediatric Hematology, Fujian Institute of Hematology, Fujian Provincial Key Laboratory on Hematology, Fujian Medical University Union Hospital , ,", "Department of Pediatrics, Nanfang Hospital, Southern Medical University , ,", "Department of Pediatric Hematology/Oncology, Hematology and Oncology, Hunan Children’s Hospital , ,", "Department of Pediatric Hematology/Oncology, Shenzhen Children’s Hospital , ,", "Department of Pediatrics, Zhujiang Hospital of Southern Medical University , ,", "Department of Pediatrics, Paediatrics, People’s Hospital of Hunan Province , ,", "Paediatrics, The First Affiliated Hospital of Xiamen University , ," ], "article_type": "research article", "arxiv": null, "author_total": 12, "authors": [ { "affs": [ 0 ], "name": "Mei Li" }, { "affs": [ 0 ], "name": "Chunxia Cai" }, { "affs": [ 0 ], "name": "Chunping Wu" }, { "affs": [ 1 ], "name": "Xiaoqin Feng" }, { "affs": [ 2 ], "name": "Mincui Zheng" }, { "affs": [ 3 ], "name": "Huirong Mai" }, { "affs": [ 4 ], "name": "Lihua Yang" }, { "affs": [ 5 ], "name": "Xiangling He" }, { "affs": [ 6 ], "name": "Hong Wen" }, { "affs": [ 0 ], "name": "Shaohua Le" }, { "affs": [ 0 ], "name": "Nainong Li" }, { "affs": [ 0 ], "name": "Yongzhi Zheng" } ], "bibtex": "https://research.draconitic.com/paper/1qbrhgmwdnxhp.bib", "cited_by": 0, "doi": "10.3389/fonc.2026.1897872", "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13661505/?tool=EBI", "id": "1qbrhgmwdnxhp", "issns": [ "2234-943X" ], "landing_url": "https://europepmc.org/article/PMC/PMC13661505", "language": "eng", "licence": "CC-BY", "licence_label": "CC BY", "licence_source": "article", "licence_url": "https://creativecommons.org/licenses/by/4.0/", "metadata_licence": null, "native_subjects": [ [ "openalex", "2720|Acute Myeloid Leukemia Research" ] ], "openalex": "W7214938832", "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13661505/pdf/?tool=EBI", "pmcid": "PMC13661505", "pmid": null, "published": "2026-09-30", "publisher": "Frontiers Media SA", "ris": "https://research.draconitic.com/paper/1qbrhgmwdnxhp.ris", "sources": [ { "first_seen": "2026-10-30T12:17:20Z", "native_id": "PMC:PMC13661505", "source": "europepmc", "url": "https://europepmc.org/article/PMC/PMC13661505" }, { "first_seen": "2026-10-30T12:20:13Z", "native_id": "10.3389/fonc.2026.1897872", "source": "crossref", "url": "https://www.frontiersin.org/articles/10.3389/fonc.2026.1897872/full" } ], "subjects": [ { "field": "medicine", "origin": "issn:2234-943X", "subfield": "oncology" } ], "title": "Fusion-specific co-mutational architecture and treatment-response associations in pediatric core-binding factor acute myeloid leukemia: a multicenter exome-profiled cohort", "title_text": "Fusion-specific co-mutational architecture and treatment-response associations in pediatric core-binding factor acute myeloid leukemia: a multicenter exome-profiled cohort", "type": "peer-reviewed", "updated_at": "2026-10-30T12:20:13Z", "url": "https://research.draconitic.com/paper/1qbrhgmwdnxhp", "venue": "Frontiers in oncology", "versions": [] }