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Spotlight on Acute Promyelocytic Leukemia

Finding a role for PML in APL pathogenesis: a critical assessment of potential PML activities

Abstract

In normal mammalian cells the promyelocytic leukemia protein (PML) is primarily localized in multiprotein nuclear complexes called PML nuclear bodies. However, both PML and PML nuclear bodies are disrupted in acute promyelocytic leukemia (APL). The treatment of APL patients with all-trans retinoic acid (ATRA) results in clinical remission associated with blast cell differentiation and reformation of the PML nuclear bodies. These observations imply that the structural integrity of the PML nuclear body is critically important for normal cellular functions. Indeed, PML protein is a negative growth regulator capable of causing growth arrest in the G1 phase of the cell cycle, transformation suppression, senescence and apoptosis. These PML-mediated, physiological effects can be readily demonstrated. However, a discrete biochemical and molecular model of PML function has yet to be defined. Upon first assessment of the current PML literature there appears to be a seemingly endless list of potential PML partner proteins implicating PML in a variety of regulatory mechanisms at every level of gene expression. The purpose of this review is to simplify this confusing field of research by using strict criteria to deduce which models of PML body function are well supported.

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Acknowledgements

SS is a fellow of the Samuel Waxman Cancer Research Foundation. KLBB is a scholar of the Leukemia and Lymphoma Society. Financial support was provided by NIH grants (CA 80728 and CA 88991).

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Strudwick, S., Borden, K. Finding a role for PML in APL pathogenesis: a critical assessment of potential PML activities. Leukemia 16, 1906–1917 (2002). https://doi.org/10.1038/sj.leu.2402724

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