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Blood, 15 March 2004, Vol. 103, No. 6, pp. 1985-1994. Prepublished online as a Blood First Edition Paper on November 20, 2003; DOI 10.1182/blood-2003-06-2126. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-06-2126v1 2003-06-2126v2 103/6/1985    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 HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Laouar, Y. Articles by Flavell, R. A. Search for Related Content PubMed PubMed Citation Articles by Laouar, Y. Articles by Flavell, R. A. Related Collections Hematopoiesis and Stem Cells Immunobiology Apoptosis Cell Cycle Plenary Papers Signal Transduction Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  PLENARY PAPERS Overexpression of IL-7R provides a competitive advantage during early T-cell development Yasmina Laouar, I. Nicholas Crispe, and Richard A. Flavell From the Section of Immunobiology, Yale University School of Medicine, New Haven, CT; David H. Smith Center for Vaccine Biology and Immunology, University of Rochester, Rochester, NY; and Howard Hughes Medical Institute, New Haven, CT. Critical checkpoints controlling early thymic T-cell development and homeostasis are set by the proper signaling function of the interleukin 7 receptor (IL-7R) and the pre–T-cell antigen receptor. Although T-cell development is observed in IL-7– and IL-7R–deficient mice, the number of thymocytes is significantly reduced, implying a role for the IL-7R in controlling the size of the thymic T-cell compartment. Here, we report the overexpression of IL-7R that occurs in the early T-cell compartment from AKR/J mice, animals that are highly susceptible to the spontaneous development of thymoma. Increased IL-7R was revealed by surface staining, and increased IL-7R mRNA was documented by using reverse transcriptase–polymerase chain reaction (RT-PCR). This resulted in increased survival of AKR/J early thymocytes, shown by the decreased frequency of TUNEL+ (terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate [dUTP]–fluorescein nick end labeling) cells. In an in vivo thymocyte repopulation model, AKR/J thymocytes had a selective advantage over healthy thymocytes. This advantage occurred at early stages of T-cell development. Our findings support the model that overexpression of growth factor receptors can contribute to proliferation and malignancy. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Can increased cytokine receptor signaling cause leukemia? Kenneth Weinberg Blood 2004 103: 1976-1977. [Full Text] [PDF] This article has been cited by other articles: S. Gonzalez-Garcia, M. Garcia-Peydro, E. Martin-Gayo, E. Ballestar, M. Esteller, R. Bornstein, J. L. de la Pompa, A. A. Ferrando, and M. L. Toribio CSL-MAML-dependent Notch1 signaling controls T lineage-specific IL-7R{alpha} gene expression in early human thymopoiesis and leukemia J. Exp. Med., April 13, 2009; 206(4): 779 - 791. [Abstract] [Full Text] [PDF] H. Yang, B. Madison, D. L. Gumucio, and D. H. Teitelbaum Specific overexpression of IL-7 in the intestinal mucosa: the role in intestinal intraepithelial lymphocyte development Am J Physiol Gastrointest Liver Physiol, June 1, 2008; 294(6): G1421 - G1430. [Abstract] [Full Text] [PDF] I. Munitic, J. A. Williams, Y. Yang, B. Dong, P. J. Lucas, N. El Kassar, R. E. Gress, and J. D. Ashwell Dynamic regulation of IL-7 receptor expression is required for normal thymopoiesis Blood, December 15, 2004; 104(13): 4165 - 4172. [Abstract] [Full Text] [PDF] J. T. Barata, A. Silva, J. G. Brandao, L. M. Nadler, A. A. Cardoso, and V. A. Boussiotis Activation of PI3K Is Indispensable for Interleukin 7-mediated Viability, Proliferation, Glucose Use, and Growth of T Cell Acute Lymphoblastic Leukemia Cells J. Exp. Med., September 7, 2004; 200(5): 659 - 669. [Abstract] [Full Text] [PDF]

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