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Blood, 15 May 2006, Vol. 107, No. 10, pp. 4115-4121. Prepublished online as a Blood First Edition Paper on January 31, 2006; DOI 10.1182/blood-2005-09-3551. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-09-3551v1 107/10/4115    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 Reschly, E. J. Articles by Kee, B. L. Search for Related Content PubMed PubMed Citation Articles by Reschly, E. J. Articles by Kee, B. L. Related Collections Apoptosis Signal Transduction Immunobiology Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Notch1 promotes survival of E2A-deficient T cell lymphomas through pre–T cell receptor–dependent and –independent mechanisms Erica J. Reschly, Christina Spaulding, Tomas Vilimas, W. Vallen Graham, Rachel L. Brumbaugh, Iannis Aifantis, Warren S. Pear, and Barbara L. Kee From the Departments of Pathology and Medicine and the Committees on Immunology and Cancer Biology, University of Chicago, Chicago IL; the Department of Pathology and Laboratory Medicine, Abramson Family Cancer Research Institute, and the Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, PA. Loss of E2A transcription factor activity or activation of the intracellular form of Notch1 (ICN) leads to the development of leukemia or lymphoma in humans or mice, respectively. Current models propose that ICN functions by suppressing E2A through a pre–T cell receptor (TCR)–dependent mechanism. Here we show that lymphomas arising in E2A–/– mice require the activation of Notch1 for their survival and have accumulated mutations in, or near, the Notch1 PEST domain, resulting in increased stability and signaling. In contrast, lymphomas arising in p53–/– mice show the activation of Notch1, but no mutations were identified in ICN. The requirement for Notch1 signaling in E2A–/– lymphomas cannot be overcome by ectopic expression of pT; however, pT is required for optimal survival and expansion of these cells. Our findings indicate that the activation of Notch1 is an important "second hit" for the transformation of E2A–/– T cell lymphomas and that Notch1 promotes survival through pre–TCR-dependent and -independent mechanisms. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: 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] K. Bessette, M. L. Lang, R. A. Fava, M. Grundy, J. Heinen, L. Horne, R. Spolski, A. Al-Shami, H. C. Morse III, W. J. Leonard, et al. A Stat5b transgene is capable of inducing CD8+ lymphoblastic lymphoma in the absence of normal TCR/MHC signaling Blood, January 1, 2008; 111(1): 344 - 350. [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. Fasseu, P. D. Aplan, M. Chopin, N. Boissel, J.-C. Bories, J. Soulier, H. von Boehmer, F. Sigaux, and A. Regnault p16INK4A tumor suppressor gene expression and CD3{epsilon} deficiency but not pre-TCR deficiency inhibit TAL1-linked T-lineage leukemogenesis Blood, October 1, 2007; 110(7): 2610 - 2619. [Abstract] [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] B. J. Thompson, S. Buonamici, M. L. Sulis, T. Palomero, T. Vilimas, G. Basso, A. Ferrando, and I. Aifantis The SCFFBW7 ubiquitin ligase complex as a tumor suppressor in T cell leukemia J. Exp. Med., August 6, 2007; 204(8): 1825 - 1835. [Abstract] [Full Text] [PDF] S. M. Chan, A. P. Weng, R. Tibshirani, J. C. Aster, and P. J. Utz Notch signals positively regulate activity of the mTOR pathway in T-cell acute lymphoblastic leukemia Blood, July 1, 2007; 110(1): 278 - 286. [Abstract] [Full Text] [PDF] Z. Guo, M. Dose, D. Kovalovsky, R. Chang, J. O'Neil, A. T. Look, H. von Boehmer, K. Khazaie, and F. Gounari {beta}-Catenin stabilization stalls the transition from double-positive to single-positive stage and predisposes thymocytes to malignant transformation Blood, June 15, 2007; 109(12): 5463 - 5472. [Abstract] [Full Text] [PDF] W. Xu and B. L. Kee Growth factor independent 1B (Gfi1b) is an E2A target gene that modulates Gata3 in T-cell lymphomas Blood, May 15, 2007; 109(10): 4406 - 4414. [Abstract] [Full Text] [PDF] V. M. Sharma, J. A. Calvo, K. M. Draheim, L. A. Cunningham, N. Hermance, L. Beverly, V. Krishnamoorthy, M. Bhasin, A. J. Capobianco, and M. A. Kelliher Notch1 Contributes to Mouse T-Cell Leukemia by Directly Inducing the Expression of c-myc Mol. Cell. Biol., November 1, 2006; 26(21): 8022 - 8031. [Abstract] [Full Text] [PDF]

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