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Development of T-cell lymphomas in Eμ-IEX-1 mice

Oncogene volume 22, pages 6845–6851 (2003)Cite this article

Abstract

Inhibition of apoptosis or abnormal cell survival can result in tumorigenesis by facilitating the insurgence of various mutations. Immediate-early response gene X-1 (IEX-1), protects T cells from apoptosis induced by the ligation of Fas or the T-cell receptor (TCR)/CD3 complex in Eμ-IEX-1 mice that direct the gene expression in both T and B cell lineages under the control of the Eμ enhancer. Consistent with a biased effect of IEX-1 towards T cells, Eμ-IEX-1 mice selectively developed T-cell lymphomas in the spleen, when they aged, which may be associated with increased levels of IEX-1 phosphorylation in T cells compared to B cells. The lymphomas were single positive (CD4+CD8−, CD4−CD8+), double positive (CD4+CD8+), or double negative (CD4−CD8−) T cells. They resulted from aberrantly clonal expansions of T cells expressing a specific TCR, as suggested by the TCR repertoire analysis using a panel of monoclonal antibodies recognizing TCR Vβ chain, as well as by TCR β gene rearrangements. The study provides, for the first time, unambiguous evidence of the oncogenic potential of IEX-1 in a cell-specific manner. The animal model may help our understanding of peripheral T-cell lymphoma development.

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Acknowledgements

We thank the staff in the Department of Pathology in the Texas Children's hospital for assistance in preparation of tissue sections and stimulating discussion. This work was supported by the National Institutes of Health Grant AI45003, Research Scholar Grant RSG-01-178-01-MGO from the American Cancer Society, and a Moran foundation award (PRJ 00-114) from the Baylor College Medicine (to MXW).

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Authors and Affiliations

  1. Department of Pathology, Baylor College of Medicine, Houston, 77030, TX

    Yujin Zhang, Milton J Finegold & Mei X Wu

  2. Department of Molecular and Cell Biology, Boston University Medical Center, Boston, 02118, MA, USA

    Yujin Zhang & Mei X Wu

  3. Department of Hematology, Institut Cochin, INSERM U567, CNRS UMR 8104, 27 rue du Fg St Jacques, Paris, 75014, France

    Françoise Porteu

  4. Department of Microbiology and Immunology, University of Illinois, Chicago, 60612, Illinois, USA

    Prasad Kanteti

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  1. Yujin Zhang
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Correspondence to Mei X Wu.

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Zhang, Y., Finegold, M., Porteu, F. et al. Development of T-cell lymphomas in Eμ-IEX-1 mice. Oncogene 22, 6845–6851 (2003). https://doi.org/10.1038/sj.onc.1206707

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