BPDCN MYB fusions regulate cell cycle genes, impair differentiation, and induce myeloid–dendritic cell leukemia

• DOI: 10.1172/jci.insight.183889
• Publication Date: 2024-11-05T21:21:07Z
• Authors: Christopher A.G. ...; Juliette M. Bouyssou; Katsuhiro Togami; Olivier Armand; Hembly G. Rivas; Kezhi Yan; Siobhan Rice; Shuyuan Cheng; Emily M. Lachtara; Jean-Pierre Bourquin; Alex Kentsis; Esther Rheinbay; James A. DeCaprio; Andrew A. Lane
• Keywords: MYB

MYB fusions are recurrently found in select cancers, including blastic plasmacytoid dendritic cell neoplasm (BPDCN), an acute leukemia with poor prognosis. They markedly enriched BPDCN compared to other blood and some patients the only obvious somatic mutation detected. This suggests they may alone be sufficient drive transformation. hypothesized alter normal transcription factor activity of MYB, but mechanistically how promote leukemogenesis is poorly understood. Using CUT&RUN chromatin profiling, we that leukemogenesis, switches from being a regulator lineage genes aberrantly regulating G2/M cycle control genes. increased magnitude DNA binding at these locations, this was linked BPDCN-associated gene expression changes. Furthermore, vivo impaired differentiation induced transformation generate mouse model myeloid-dendritic leukemia. Therapeutically, present evidence all-trans retinoic acid (ATRA) cause loss protein death BPDCN.