PML Nuclear bodies: the cancer connection and beyond

Abstract

Promyelocytic leukemia (PML) nuclear bodies, membrane-less organelles in the nucleus, play a crucial role in cellular homeostasis. These dynamic structures result from the assembly of scaffolding PML proteins and various partners. Recent crystal structure analyses revealed essential self-interacting domains, while liquid–liquid phase separation contributes to their formation. PML bodies orchestrate post-translational modifications, particularly stress-induced SUMOylation, impacting target protein functions. Serving as hubs in multiple signaling pathways, they influence cellular processes like senescence. Dysregulation of PML expression contributes to diseases, including cancer, highlighting their significance. Therapeutically, PML bodies are promising targets, exemplified by successful acute promyelocytic leukemia treatment with arsenic trioxide and retinoic acid restoring PML bodies. Understanding their functions illuminates both normal and pathological cellular physiology, guiding potential therapies. This review explores recent advancements in PML body biogenesis, biochemical activity, and their evolving biological roles.

Nuclear bodies: a gene expression collection for our time

“…The article by Majdouline Abou-Ghali and Valerie Lallemand-Breitenbach on PML bodies [ 8 ] complements the one on the PNC in that these bodies were also discovered years ago but acquired a functional connection only later, when their presence was noted to be correlated with cancer cells and, in particular, was related to an oncogenic fusion of a PML body protein gene with that encoding the retinoic acid A receptor. The authors engagingly describe this evolution as well as the particular connection of PML bodies to hematological cancers.…”