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Blood, 1 January 2008, Vol. 111, No. 1, pp. 344-350. Prepublished online as a Blood First Edition Paper on September 21, 2007; DOI 10.1182/blood-2007-04-084707. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2007-04-084707v1 111/1/344    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Bessette, K. Articles by Kelly, J. A. Search for Related Content PubMed PubMed Citation Articles by Bessette, K. Articles by Kelly, J. A. Related Collections Neoplasia Oncogenes and Tumor Suppressors Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA A Stat5b transgene is capable of inducing CD8+ lymphoblastic lymphoma in the absence of normal TCR/MHC signaling Katherine Bessette1,2, Mark L. Lang3, Roy A. Fava13, Martin Grundy1, Jennifer Heinen1, Laurie Horne3, Rosanne Spolski4, Amin Al-Shami4, Herbert C. Morse, III5, Warren J. Leonard4, and John A. Kelly13 1 White River Junction Veteran's Association, White River Junction, VT; 2 Department of Medicine and 3 Department of Micro/Immunology, Dartmouth Medical School, Lebanon, NH; 4 Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, Bethesda, MD; and 5 Laboratory of Immunopathology, National Institute of Allergy and Infectious Diseases, Rockville, MD Stat5 proteins are critical signaling molecules activated by many cytokines. Within the immune system, Stat5 plays important roles related to the development of thymocytes and proliferation of T cells. Stat5 has been implicated in malignant transformation, and moreover, the activated tyrosine phosphorylated form of Stat5 is frequently observed in human lymphomas. We previously demonstrated the oncogenic potential of Stat5, with thymic lymphoblastic lymphomas developing in a significant proportion of transgenic (TG) mice overexpressing Stat5a or Stat5b in lymphocytes. In addition, immunization or expression of a T-cell receptor (TCR) transgene augmented the rate of tumor formation. Here, we investigate the mechanism of Stat5-mediated lymphomagenesis by exploring the contributions of major histocompatibility complex (MHC)/TCR and pre-TCR signals. We present data demonstrating that Stat5b TG mice unexpectedly develop CD8+ lymphoma even in the absence of either pre-TCR signaling or normal thymic selection. Indeed, acceleration of Stat5b transgene-mediated lymphoma occurred on TCR–/– and pre-TCR–/– backgrounds. In light of these data, we propose a model in which alterations in T-cell development at the double-negative/double-positive (DN/DP) stages cooperate with cytokine-mediated pathways in immature thymocytes to give rise to lymphoblastic T-cell lymphomas in Stat5b TG mice. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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