GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE328nnn/GSE328418/primaryOK200GenomicsHomo sapiensGenome binding/occupancy profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE328418GEOGSEfalseCBFA2T3-GLIS2 fusion-mediated mSWI/SNF chromatin remodeler disruption generates cancer-specific dependencies in AMKL [Cut&Tag WSU-AML]Transcription factor (TF) fusion oncoproteins are frequently associated with poor prognosis and remain challenging therapeutic targets. Here we show that the CBFA2T3-GLIS2 (C/G) fusion oncoprotein present in lethal pediatric acute megakaryocytic leukemias (AMKLs) co-opts mSWI/SNF chromatin remodeling complexes, reprogramming regulatory element architecture to sustain aberrant cell cycle progression. The C/G fusion binds to and redistributes mSWI/SNF complexes via the SMARCD1 SWIFT domain and targets complexes to oncogenic enhancers including those bound by ETS family TFs and the G1 cyclin CCND2, a C/G AML-specific dependency. Pharmacologic inhibition of mSWI/SNF-mediated G1 cell cycle phasing via FHD-286 suppresses C/G-driven gene expression programs, induces G1 arrest and apoptosis in cells, and reduces leukemic burden and extends survival in aggressive C/G AML in vivo. These findings define an oncogenic mSWI/SNF–G1 axis in C/G AML and establish a therapeutic framework for targeting chromatin dysfunction-mediated cell cycle aberrancy in high-risk pediatric leukemias.2026/04/22GSE328418GSM9682512GSM9682513GSM9682510GSM9682499GSM9682511GSM9682497GSM9682498GSM9682509GSM9682507GSM9682508GSM9682505GSM9682506GSM9682503GSM9682504GSM9682501GSM9682502GSM9682521GSM9682500GSM9682520GSM9682518GSM9682519GSM9682516GSM9682517GSM9682514GSM968251534284328418Homo sapiens