Open Access
Article
PML nuclear bodies in the pathogenesis of acute promyelocytic leukemia: active players or innocent bystanders?
Nicola J M Brown1,Michal Ramalho1,Eva W Pedersen1,Eva Moravcsik1,Ellen Solomon1,David Grimwade1
1
Department of Medical and Molecular Genetics, King's College London School of Medicine, London, UK
DOI: 10.2741/3333 Volume 14 Issue 5, pp.1684-1707
Published: 01 January 2009
Abstract

The promyelocytic leukemia gene (PML) encodes a protein which localizes to PML-nuclear bodies (NBs), sub-nuclear multi-protein structures, which have been implicated in diverse biological functions such as apoptosis, cell proliferation and senescence. However, the exact biochemical and molecular basis of PML function up until now has not been defined. Strikingly, over a decade ago, PML-NBs were found to be disrupted in acute promyelocytic leukemia (APL) in which PML is fused to the gene encoding retinoic acid receptor alpha (RARA) due to the t(15;17) chromosomal translocation, generating the PML-RARA chimeric protein. The treatment of APL patients with all-transretinoic acid (ATRA) and arsenic trioxide which target the PML-RARA oncoprotein results in clinical remission, associated with blast cell differentiation and reformation of the PML NBs, thus linking NB integrity with disease status. This review focuses on the current theories for molecular and biochemical functions of the PML-NBs, which would imply a role in the pathogenesis of APL, whilst also discussing the intriguing possibility that their disruption may not be in itself a significant oncogenic event.

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Nicola J M Brown, Michal Ramalho, Eva W Pedersen, Eva Moravcsik, Ellen Solomon, David Grimwade. PML nuclear bodies in the pathogenesis of acute promyelocytic leukemia: active players or innocent bystanders?. Frontiers in Bioscience-Landmark. 2009. 14(5); 1684-1707.