Mutant ASXL1 Cooperates with MECOM and BRD4 to Drive Transcriptional Dysregulation in Human Hematopoiesis

The authors investigate how mutations in the epigenetic regulator ASXL1 contribute to transcriptional dysregulation in human hematopoietic stem cells, which is critical for understanding the poor prognosis associated with ASXL1 mutations in myeloid malignancies. They demonstrate that mutant ASXL1 leads to decreased differentiation and increased clonogenicity, driven by altered transcriptional dynamics and interactions with MECOM and BRD4. This study provides a functional characterization of the ASXL1 mutant interactome, highlighting potential therapeutic targets for ASXL1-mutant myeloid cancers.