The PML hub: An emerging actor of leukemia therapies

Abstract

PML assembles into nuclear domains that have attracted considerable attention from cell and cancer biologists. Upon stress, PML nuclear bodies modulate sumoylation and other post-translational modifications, providing an integrated molecular framework for the multiple roles of PML in apoptosis, senescence, or metabolism. PML is both a sensor and an effector of oxidative stress. Emerging data has demonstrated its key role in promoting therapy response in several hematological malignancies. While these membrane-less nuclear hubs can enforce efficient cancer cell clearance, their downstream pathways deserve better characterization. PML NBs are druggable and their known modulators may have broader clinical utilities than initially thought.

Structural Basis of PML-RARA Oncoprotein Targeting by Arsenic Unravels a Cysteine Rheostat Controlling PML Body Assembly and Function

“…PML is involved in oxidative stress responses ( 50, 51 ), notably in hepatocytes ( 46 ). To explore any role of B2 trimerization, we engineered a Pml A220V knock-in mice (corresponding to the A216V hotspot mutation in the human sequence).…”

PML Nuclear bodies: the cancer connection and beyond

“…PML bodies have been extensively investigated in cancer research, especially acute myeloid leukemia (AML) and acute promyelocytic leukemia (APL). Several therapies for APL have emerged, implicating nuclear bodies, as reviewed recently [ 8 ]. We will approach the formation of PML bodies, their importance, and molecular modifications, and end by shedding light on some of the various roles they play in different processes in the cell.…”