FBS Colloquia No.398Laboratory of Cancer Pathology

The Role of Bromodomain-Containing Protein BRD9 in Hematopoiesis and Leukemogenesis

Hematopoietic stem cells (HSCs) constitute the apex of the hematopoietic hierarchy, orchestrating the generation of all blood cell lineages while preserving their self-renewal capacity through tightly regulated multipotent differentiation programs. The fidelity of HSC function is contingent upon the precise orchestration of transcriptional networks mediated by epigenetic chromatin remodeling complexes, whose perturbation invariably precipitates malignant transformation. In this colloquium, I will present the multifaceted roles of BRD9, a bromodomain-containing protein involved in chromatin remodeling, in regulating HSC maintenance, lineage specification, and malignant transformation. Furthermore, I will delineate the pathogenic mechanisms underlying the BRD9–NUTM1 fusion oncogene, which aberrantly recruits the transcriptional co-activator p300 and constitutes a defining molecular signature of infant acute leukemia.