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ETS1 recruits cBAF to hijack the hematopoietic stem cell MYB enhancer in T-cell leukemia [dataset 1]

GSE263585 Homo sapiens Genome binding/occupancy profiling by high throughput sequencing 4 samples Submitted 2025/09/25 Platform GPL21697
Summary
Notch signaling is the most prevalent oncogenic pathway in T-ALL, but clinical trials showed that pan-Notch inhibitors caused dose-limiting toxicities. Thus, we shifted our focus from Notch to ETS1, which is one of the top transcription factors that most frequently co-bind Notch-occupied regulatory elements in the T-ALL context. A top essential ETS1-dependent element was a Notch-bound enhancer at +140kb from MYB that we named the ETS-MYB enhancer (E-Me). Using genetically engineered mouse models and chromatin profiling, we showed that the E-Me selectively promotes self-renewal of hematopoietic stem cells, becomes inactive in committed T cell progenitors; and is reactivated to promote Notch-induced transformation.
Published in
The hematopoietic stem cell MYB enhancer is essential for and recurrently amplified during T cell leukemogenesis
Mullin C, Lin K, Choe E et al. · The Journal of clinical investigation 2026 · PMID 41129262 · doi:10.1172/JCI187998
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Also filed as BioProject PRJNA1098213 and SRA study SRP500592. Searching any of these in the dataset finder brings you back here.

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