Condensates in fusion oncoprotein-driven leukemia: new biology and therapeutic opportunities.

Chromosomal rearrangements leading to the formation of fusion oncoproteins (FOs) are drivers of leukemia and other cancers. Many such FOs are now known to localize in nuclear or cytoplasmic condensates formed through the process of phase separation (PS). FO-associated condensates facilitate the spatiotemporal organization of key macromolecules required for oncogenic transformation. NUP98 fusions provided the first example of FO-associated condensates in leukemia, and other leukemic drivers subsequently illustrated the shared and distinct mechanisms by which PS contributes to leukemogenesis. Improved understanding of FO-associated condensates has, in turn, revealed new opportunities for therapeutic targeting. Pharmacologic approaches, including the dissolution of condensates, inhibition of key condensate components, or modification of condensate material properties, may translate to more effective treatments for patients with FO-driven cancer.