Since the discovery of Promyelocytic leukemia (PML), this protein has been associated with the pathogenesis of several hematopoietic malignancies and solid tumors. PML was first identified as part of a fusion oncoprotein, PML-RARα, responsible for the development of acute promyelocytic leukemia (APL)( 1–4). The PML-RARα fusion protein not only alters PML function but also represses transcriptional activity mediated by RARRXR, thereby disrupting retinoid signaling, inhibiting myeloid differentiation and enhancing the survival and proliferation of early myeloid progenitors (5). Loss of PML in cancers from multiple origins underlines its tumor-suppressive role beyond leukemia ( 6).

Since PML seemed to be a key regulator underlying leukemia and other cancers, these initial findings motivated a series of studies aimed at ascertaining its regulatory cues and functions. It is now well established that PML is the building block of the PML-nuclear bodies (PML-NBs). PML functions as a protein scaffold and interaction partner for a growing number of factors that shuttle in and out of these structures in a highly regulated process ( 7–9).