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Spotlight on Acute Promyelocytic Leukemia

PML a target of translocations in APL is a regulator of cellular senescence

Leukemia volume 16, pages 1918–1926 (2002)Cite this article

Abstract

PML is the most frequent fusion partner of the RARα in the specific translocations associated with acute promyelocytic leukemia (APL). Models to explain the origin of this leukemia propose a block in cell differentiation due to aberrant repression of retinoic acid responsive genes and/or disruption of the function of the PML-containing nuclear bodies. Recently, PML has been identified as a regulator of replicative senescence and the premature senescence that occurs in response to oncogenic ras. This review discusses the idea that senescence is a general tumor suppressor mechanism related to terminal differentiation and disrupted during the establishment of APL and other cancers. According to this idea the PML-RARα fusion protein promotes leukemogenesis not only through repression of retinoic acid responsive genes, but also by way of interfering with several tumor suppressor proteins that cooperate to establish senescence. Retinoids and other drugs effective against APL do so by re-establishment of the senescence program, which also includes features of cell differentiation.

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Acknowledgements

GF is a fellow of the Canadian Institute of Health and Research. I thank Drs Clemens Schmitt and Ari Melnick for valuable comments on this manuscript and V Bourdeau for help with the figures. The ideas presented in this review were motivated in the excellent scientific environment of the laboratory of Scott Lowe at Cold Spring Harbor. I thank Dr Lowe and the members of his laboratory for discussions.

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  1. Département de Biochimie, Université de Montréal, Montréal, Canada

    G Ferbeyre

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Ferbeyre, G. PML a target of translocations in APL is a regulator of cellular senescence. Leukemia 16, 1918–1926 (2002). https://doi.org/10.1038/sj.leu.2402722

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  • DOI: https://doi.org/10.1038/sj.leu.2402722

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