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Blood, 15 June 2007, Vol. 109, No. 12, pp. 5463-5472. Prepublished online as a Blood First Edition Paper on February 22, 2007; DOI 10.1182/blood-2006-11-059071. This Article Full Text Full Text (PDF) Supplemental Tables and Figures All Versions of this Article: blood-2006-11-059071v1 109/12/5463    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 Guo, Z. Articles by Gounari, F. Search for Related Content PubMed PubMed Citation Articles by Guo, Z. Articles by Gounari, F. Related Collections Immunobiology Neoplasia Signal Transduction Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA ß-Catenin stabilization stalls the transition from double-positive to single-positive stage and predisposes thymocytes to malignant transformation Zhuyan Guo1, Marei Dose1, Damian Kovalovsky1, Rui Chang1, Jennifer O'Neil2, A. Thomas Look2, Harald von Boehmer2, Khashayarsha Khazaie2,3, and Fotini Gounari1 1 Molecular Oncology Research Institute, Tufts-New England Medical Center, Boston; 2 Dana-Farber Cancer Institute, Harvard Medical School, Boston; 3 Center for Molecular Imaging Research, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA Activation of ß-catenin has been causatively linked to the etiology of colon cancer. Conditional stabilization of this molecule in pro-T cells promotes thymocyte development without the requirement for pre-TCR signaling. We show here that activated ß-catenin stalls the developmental transition from the double-positive (DP) to the single-positive (SP) thymocyte stage and predisposes DP thymocytes to transformation. ß-Catenin–induced thymic lymphomas have a leukemic arrest at the early DP stage. Lymphomagenesis requires Rag activity, which peaks at this developmental stage, as well as additional secondary genetic events. A consistent secondary event is the transcriptional up-regulation of c-Myc, whose activity is required for transformation because its conditional ablation abrogates lymphomagenesis. In contrast, the expression of Notch receptors as well as targets is reduced in DP thymocytes with stabilized ß-catenin and remains low in the lymphomas, indicating that Notch activation is not required or selected for in ß-catenin–induced lymphomas. Thus, ß-catenin activation may provide a mechanism for the induction of T-cell–acute lymphoblastic leukemia (T-ALL) that does not depend on Notch activation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Uncontrolled Wnt signaling causes leukemia Frank J. T. Staal Blood 2007 109: 5073-5074. [Full Text] [PDF] This article has been cited by other articles: D. Kovalovsky, Y. Yu, M. Dose, A. Emmanouilidou, T. Konstantinou, K. Germar, K. Aghajani, Z. Guo, M. Mandal, and F. Gounari {beta}-Catenin/Tcf Determines the Outcome of Thymic Selection in Response to {alpha}{beta}TCR Signaling J. Immunol., September 15, 2009; 183(6): 3873 - 3884. [Abstract] [Full Text] [PDF] M. Haldar, M. L. Hedberg, M. F. Hockin, and M. R. Capecchi A CreER-Based Random Induction Strategy for Modeling Translocation-Associated Sarcomas in Mice Cancer Res., April 15, 2009; 69(8): 3657 - 3664. [Abstract] [Full Text] [PDF] R. W.J. Groen, M. E.C.M. 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