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Oncogenes, Fusion Genes And Tumor Suppressor Genes

Leukemia suppressor function of Egr-1 is dependent on transforming oncogene

Leukemia volume 22, pages 1909–1916 (2008)Cite this article

Abstract

We have shown that deregulated expression of either c-Myb or E2F-1 blocks terminal differentiation of M1 myeloid leukemia cells at the blast stage, whereas deregulated c-Myc blocks differentiation at the intermediate stage. Each of these oncogenes potentiates M1 leukemia in vivo. The zinc-finger transcription factor Egr-1 abrogates the block in M1 terminal differentiation imparted by oncogenic c-Myc or E2F-1, suppressing their leukemia-promoting function in nude mice. In this study, we asked whether Egr-1 also abrogates the block in terminal differentiation and suppresses leukemia imparted by deregulated c-Myb. Interestingly, the ectopic expression of Egr-1 in M1 cells expressing deregulated c-Myb only partially abrogated the block in terminal differentiation and did not suppress the leukemic phenotype. Two important implications from these data are that the leukemia suppressor function of Egr-1 is not directly related to how early the transforming oncogene blocks the differentiation program and that the tumor suppressor function of Egr-1 is dependent on the specific oncogene. Egr-1 is dominant to c-Myc- and E2F-1-, but not to c-Myb-, driven leukemia. These findings extend the notion that the molecular nature of genetic lesions responsible for leukemia determines the effectiveness of any given tumor suppressor.

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Acknowledgements

This work was supported by a grant from the National Institutes of Health (RO1 CA081168) to BH.

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Authors and Affiliations

  1. Fels Institute for Cancer Research and Molecular Biology, Temple University, Philadelphia, PA, USA

    J D Gibbs, D A Liebermann & B Hoffman

  2. Department of Biochemistry, Temple University, Philadelphia, PA, USA

    D A Liebermann & B Hoffman

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  1. J D Gibbs
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  2. D A Liebermann
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  3. B Hoffman
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Correspondence to B Hoffman.

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Gibbs, J., Liebermann, D. & Hoffman, B. Leukemia suppressor function of Egr-1 is dependent on transforming oncogene. Leukemia 22, 1909–1916 (2008). https://doi.org/10.1038/leu.2008.189

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