Abstract 1197 Unleashed Condensation by Mutations of an Epigenetic Regulator Promotes Cancer

ASXL1 is an obligate co-factor for the BAP1 enzyme that removes H2AK119 ubiquitination, an epigenetic modification associated with gene repression. ASXL1 is frequently mutated in all forms of myeloid malignancies and clonal hematopoiesis as well as in Bohring-Opitz syndrome, a developmental disorder. ASXL1 mutations are concentrated in a central intrinsically disordered region (IDR) and often truncate the protein. ASXL1 truncations are gain-of-function mutations that promote myeloid malignancies, but the underlying mechanisms remain poorly understood.