GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE328nnn/GSE328419/primaryOK200GenomicsHomo sapiensGenome binding/occupancy profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE328419GEOGSEfalseCBFA2T3-GLIS2 fusion-mediated mSWI/SNF chromatin remodeler disruption generates cancer-specific dependencies in AMKL [Cut & Run M-07e]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.2026/04/22GSE328419GSM9682534GSM9682535GSM9682554GSM9682532GSM9682555GSM9682533GSM9682552GSM9682530GSM9682531GSM9682553GSM9682550GSM9682551GSM9682529GSM9682549GSM9682527GSM9682528GSM9682547GSM9682525GSM9682526GSM9682548GSM9682523GSM9682545GSM9682546GSM9682524GSM9682543GSM9682544GSM9682522GSM9682541GSM9682542GSM9682540GSM9682538GSM9682539GSM9682536GSM968253734284328419Homo sapiens