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Transcriptional regulation in acute promyelocytic leukemia

Oncogene volume 20, pages 7204–7215 (2001)Cite this article

Abstract

It has been 10 years since the seminal discovery that a mutant form of a retinoid acid receptor (RARα) is associated with acute promyelocytic leukemia (APL). This finding, coupled with the remarkable success of retinoic acid (RA), the natural ligand of RARα, in the treatment of APL, has made APL a unique model system in the study of oncogenic conversion of transcription factors in hematological malignancies. Indeed, subsequent basic and clinical studies showed that chromosomal translocation involving the RARα gene is the cytogenetic hallmark of APL and that these mutant forms of RARs are the oncogenes in APL that interfere with the proliferation and differentiation pathways controlled by both RAR and their fusion partners. However, it was not until recently that the role of aberrant transcriptional regulation in the pathogenesis of APL was revealed. In this review, we summarize the biochemical and biological mechanisms of transcriptional regulation by mutant RARs and their corresponding wild-type fusion partner PML and PLZF. These studies have been instrumental in our understanding of the process of leukemogenesis in general and have laid the scientific foundation for the novel concept of transcription therapy in the treatment of human cancer.

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Acknowledgements

We thank Dr Chih-hao Lee and Russell Nofsinger for discussion and comments on the manuscript. We thank D Tenen for communication of unpublished results. We apologize to all whose work we did not cite due to space limitations. RM Evans is an Investigator of the Howard Hughes Medical Institute at the Salk Institute for Biological Studies and March of Dimes Chair in Molecular Developmental Biology. This work was supported by the HHMI, NIH, Harry B Boyce Trust, and the Joe W and Dorothy Dorsett Brown Foundation.

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    Richard J Lin, Thomas Sternsdorf, Marc Tini & Ronald M Evans

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Lin, R., Sternsdorf, T., Tini, M. et al. Transcriptional regulation in acute promyelocytic leukemia. Oncogene 20, 7204–7215 (2001). https://doi.org/10.1038/sj.onc.1204853

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