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Lymphoma

Gadd45a acts as a modifier locus for lymphoblastic lymphoma

Leukemia volume 19, pages 847–850 (2005)Cite this article

Abstract

Gadd45a−/− and p53−/− mice and cells derived from them share similar phenotypes, most notably genomic instability. However, p53−/− mice rapidly develop a variety of neoplasms, while Gadd45a−/− mice do not. The two proteins are involved in a regulatory feedback loop, whereby each can increase the expression or activity of the other, suggesting that common phenotypes might result from similar molecular mechanisms. Mice lacking both genes were generated to address this issue. Gadd45a−/−p53−/− mice developed tumors with a latency similar to that of tumor-prone p53−/− mice. However, while p53−/− mice developed a variety of tumor types, nearly all Gadd45a−/−p53−/− mice developed lymphoblastic lymphoma (LBL), often accompanied by mediastinal masses as is common in human patients with this tumor type. Deletion of Gadd45a in leukemia/lymphoma-prone AKR mice decreased the latency for LBL. These results indicate that Gadd45a may act as modifier locus for T-cell LBL, whereby deletion of Gadd45a enhances development of this tumor type in susceptible mice. Gadd45a is localized to 1p31.1, and 1p abnormalities have been described in T-cell lymphomas. Related human tumor samples did not show Gadd45a deletion or mutation, although changes in expression could not be ruled out.

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Acknowledgements

This project has been funded in whole or in part with Federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. N01-C0-12400.

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Authors and Affiliations

  1. Gene Response Section, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

    M C Hollander, A D Patterson, J M Salvador & A J Fornace Jr

  2. National Institutes of Health-George Washington University Graduate Partnerships Program in Genetics,

    A D Patterson

  3. SAIC, NCI-Frederick, PO Box B, Frederick, MD, USA

    M R Anver

  4. Department of Pediatrics, University of Florida College of Medicine, Gainesville, FL, USA

    S P Hunger

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  1. M C Hollander
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  2. A D Patterson
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  3. J M Salvador
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  4. M R Anver
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  5. S P Hunger
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  6. A J Fornace Jr
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Correspondence to M C Hollander.

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Hollander, M., Patterson, A., Salvador, J. et al. Gadd45a acts as a modifier locus for lymphoblastic lymphoma. Leukemia 19, 847–850 (2005). https://doi.org/10.1038/sj.leu.2403711

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