The Journal of Experimental Medicine
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Published online 30 June 2003 doi:10.1084/jem.20021548
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© Rockefeller University Press, 0022-1007/2003/7/79 $5.00
The Journal of Experimental Medicine, Volume 198, Number 1, 79-89

Stat5 Synergizes with T Cell Receptor/Antigen Stimulation in the Development of Lymphoblastic Lymphoma

John A. Kelly1, Rosanne Spolski1, Panu E. Kovanen1, Takeshi Suzuki3, Julie Bollenbacher1, Cynthia A. Pise-Masison3, Michael F. Radonovich2, Stephen Lee1, Nancy A. Jenkins3, Neal G. Copeland3, Herbert C. Morse, III4 and Warren J. Leonard1

1 Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute
2 Laboratory of Receptor Biology and Gene Expression, National Cancer Institute, Bethesda, MD 20892
3 Mouse Cancer Genetics Program, National Cancer Institute-Frederick, Frederick, MD 21702
4 The Laboratory of Immunopathology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852

Address correspondence to W.J. Leonard, Bldg. 10, Rm. 7N252, Laboratory of Molecular Immunology, NHLBI, NIH, Bethesda, MD 20892-1674. Phone: 301-496-0098; Fax: 301-402-0971; E-mail: wjl{at}helix.nih.gov

Signal transducer and activator of transcription (STAT) proteins are latent transcription factors that mediate a wide range of actions induced by cytokines, interferons, and growth factors. We now report the development of thymic T cell lymphoblastic lymphomas in transgenic mice in which Stat5a or Stat5b is overexpressed within the lymphoid compartment. The rate of lymphoma induction was markedly enhanced by immunization or by the introduction of TCR transgenes. Remarkably, the Stat5 transgene potently induced development of CD8+ T cells, even in mice expressing a class II–restricted TCR transgene, with resulting CD8+ T cell lymphomas. These data demonstrate the oncogenic potential of dysregulated expression of a STAT protein that is not constitutively activated, and that TCR stimulation can contribute to this process.

Key Words: Stat5 • TCR • lymphoma • DNA microarray • CD8+ T cell


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