SEARCH:   Advanced

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 (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 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 Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted November 27, 2006 Accepted February 15, 2007 -Catenin stabilization stalls the transition from Double-Positive to Single Positive stage and predisposes thymocytes to malignant transformation Zhuyan Guo, Marei Dose, Damian Kovalovsky, Rui Chang, Jennifer O'Neil, A. Thomas Look, Harald von Boehmer, Khashayarsha Khazaie, and Fotini Gounari* Molecular Oncology Research Institute, Tufts-New England Medical Center, Boston, MA, United States Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, United States Center for Molecular Imaging Research, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, United States * Corresponding author; email: fgounari{at}tufts-nemc.org. Activation of -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 preTCR signaling. We show here that activated -catenin stalls the developmental transition from the double-positive (DP) to the single-positive (SP) thymocyte stage and predisposes DP thymocytes to transformation. -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 upregulation of c-Myc, whose activity is required for transformation since its conditional ablation abrogates lymphomagenesis. In contrast, the expression of Notch receptors as well as targets is reduced in DP thymocytes with stabilized -catenin and remains low in the lymphomas indicating that Notch activation is not required or selected for in -catenin induced lymphomas. Thus, -catenin activation may provide a mechanism for the induction of 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. Oud, E. J.M. Schilder-Tol, M. B. Overdijk, D. ten Berge, R. Nusse, M. Spaargaren, and S. T. Pals Illegitimate WNT Pathway Activation by {beta}-Catenin Mutation or Autocrine Stimulation in T-Cell Malignancies Cancer Res., September 1, 2008; 68(17): 6969 - 6977. [Abstract] [Full Text] [PDF] F. J.T. Staal and A. W. Langerak Signaling pathways involved in the development of T-cell acute lymphoblastic leukemia Haematologica, April 1, 2008; 93(4): 493 - 497. [Full Text] [PDF] M. Xu, Q. Yu, R. Subrahmanyam, M. J. Difilippantonio, T. Ried, and J. M. Sen {beta}-Catenin Expression Results in p53-Independent DNA Damage and Oncogene-Induced Senescence in Prelymphomagenic Thymocytes In Vivo Mol. Cell. Biol., March 1, 2008; 28(5): 1713 - 1723. [Abstract] [Full Text] [PDF] L. M. Stephenson, B. Sammut, D. B. Graham, J. Chan-Wang, K. L. Brim, A. S. Huett, A. V. Miletic, T. Kloeppel, A. Landry, R. Xavier, et al. DLGH1 Is a Negative Regulator of T-Lymphocyte Proliferation Mol. Cell. Biol., November 1, 2007; 27(21): 7574 - 7581. [Abstract] [Full Text] [PDF] F. Gounari and M. Dose Lef-1: NOTCHed up in T-cell lymphomas Blood, October 1, 2007; 110(7): 2227 - 2227. [Full Text] [PDF] M. van Noort, F. Weerkamp, H. C. Clevers, and F. J. T. Staal Wnt signaling and phosphorylation status of {beta}-catenin: importance of the correct antibody tools Blood, October 1, 2007; 110(7): 2778 - 2779. [Full Text] [PDF] C. Spaulding, E. J. Reschly, D. E. Zagort, Y. Yashiro-Ohtani, L. J. Beverly, A. Capobianco, W. S. Pear, and B. L. Kee Notch1 co-opts lymphoid enhancer factor 1 for survival of murine T-cell lymphomas Blood, October 1, 2007; 110(7): 2650 - 2658. [Abstract] [Full Text] [PDF] J. P. Radich The Biology of CML Blast Crisis Hematology, January 1, 2007; 2007(1): 384 - 391. [Abstract] [Full Text] [PDF]

	Copyright © 2007 by American Society of Hematology         Online ISSN: 1528-0020