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Spotlight on Acute Promyelocytic Leukemia

Signaling revisited in acute promyelocytic leukemia

Leukemia volume 16, pages 1933–1939 (2002)Cite this article

Abstract

Although transcription factors are still the main focus to understanding leukemogenesis, recent results strongly suggest that alteration of a receptor and/or subsequent signaling plays a critical and co-operative role in the pathogenesis of acute myeloid leukemia (AML). The t(15;17) translocation, found in 95% of APL, encodes a PML-RARα fusion protein. A main model proposed for acute promyelocytic leukemia (APL) is that PML-RARα exerts its oncogenic effects by repressing retinoic acid-inducible genes critical to myeloid differentiation. Dysregulation of these genes may result in abnormal signaling, thereby freeing pre-leukemic cells from controls which normally induce the onset of differentiation. It is also likely that treatment of APL cells by retinoic acid induces de novo up-regulation of the same genes which are dominantly repressed by PML-RARα and whose expression is required for reactivation of the differentiation program. Identification of such genes together with the signaling pathways interrupted at the early stages of leukemia transformation and reactivated during retinoic acid-induced differentiation in APL cells will contribute to the development of new molecular targets for treatment of leukemia.

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Acknowledgements

We are indebted to all the members of our group for helpful discussions and contribution. Work in our laboratory was supported by INSERM, CNRS, and grants from the Association pour la Recherche sur le Cancer, the Fondation de France, the Comité de Paris de La Ligue Contre le Cancer, the Lady Tata Memorial Trust, and the Leukemia Research Foundation.

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  1. Unité INSERM U417, Hôpital Saint Antoine, Paris, France

    PG Lutz, C Moog-Lutz & YE Cayre

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  1. PG Lutz
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  2. C Moog-Lutz
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Lutz, P., Moog-Lutz, C. & Cayre, Y. Signaling revisited in acute promyelocytic leukemia. Leukemia 16, 1933–1939 (2002). https://doi.org/10.1038/sj.leu.2402728

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