{"database":"GEO","file_versions":[],"scores":null,"additional":{"omics_type":["Genomics"],"species":["Homo sapiens"],"gds_type":["Genome binding/occupancy profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE328504"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"CBFA2T3-GLIS2 fusion-mediated mSWI/SNF chromatin remodeler disruption generates cancer-specific dependencies in AMKL [ATAC-Seq]","description":"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.","dates":{"publication":"2026/04/22"},"accession":"GSE328504","cross_references":{"GSM":["GSM9684526","GSM9684525","GSM9684524","GSM9684523","GSM9684522","GSM9684521","GSM9684520","GSM9684519","GSM9684518","GSM9684517","GSM9684516"],"GPL":["34281"],"GSE":["328504"],"taxon":["Homo sapiens"]}}