1. ¹MRC Toxicology Unit, Lancaster Road Box 138, Leicester, LE 9HN, UK;
2. ²Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK;
3. ³Institute of Comparative Medicine, Faculty of Veterinary Medicine, 464 Bearsden Road, Glasgow G61 1QH, Scotland

Correspondence: P Salomoni, E-mail: ps90@le.ac.uk

Abstract

The PML gene is involved in the t(15;17) translocation of acute promyelocytic leukaemia (APL), which generates the oncogenic fusion protein PML (promyelocytic leukaemia protein)-retinoic acid receptor alpha. The PML protein localises to a subnuclear structure called the PML nuclear domain (PML-ND), of which PML is the essential structural component. In APL, PML-NDs are disrupted, thus implicating these structures in the pathogenesis of this leukaemia. Unexpectedly, recent studies indicate that PML and the PML-ND play a tumour suppressive role in several different types of human neoplasms in addition to APL. Because of PML's extreme versatility and involvement in multiple cellular pathways, understanding the mechanisms underlying its function, and therefore role in tumour suppression, has been a challenging task. In this review, we attempt to critically appraise the more recent advances in this field and propose new avenues of investigation.