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Blood, 1 October 2007, Vol. 110, No. 7, pp. 2610-2619. Prepublished online as a Blood First Edition Paper on May 16, 2007; DOI 10.1182/blood-2007-01-066209. This Article Full Text (PDF) Supplemental Methods and Table All Versions of this Article: blood-2007-01-066209v1 110/7/2610    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 Fasseu, M. Articles by Regnault, A. Search for Related Content PubMed PubMed Citation Articles by Fasseu, M. Articles by Regnault, A. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted January 4, 2007 Accepted April 10, 2007 p16INK4A tumor suppressor gene expression and CD3epsilon deficiency but not preTCR deficiency inhibit TAL1-linked T-lineage leukemogenesis Magali Fasseu, Peter D Aplan, Martine Chopin, Nicolas Boissel, Jean-Christophe Bories, Jean Soulier, Harald von Boehmer, Francois Sigaux, and Armelle Regnault* INSERM U462, Institut Universitaire d'Hematologie, Hopital Saint-Louis, Paris, France Genetics Branch, Center for Cancer Research, NCI, NIH, Besthesda, MD, United States INSERM U662, Institut Universitaire d'Hematologie, Hopital Saint-Louis, Paris, France EA3963-Universite Paris 7-Denis Diderot-INSERM, Institut Universitaire d'Hematologie, Hopital Saint-Louis, Paris, France Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, United States * Corresponding author; email: armelle.regnault{at}wanadoo.fr. Inactivation of the CDKN2 gene which encodes the P16INK4A and p14ARF proteins occurs in the majority of human T-cell acute lymphoblastic leukemias (T-ALL). Ectopic expression of TAL1 and LMO1 genes is linked to the development of T-ALL in humans. In TAL1xLMO1 mice, leukemia develops in 100% of mice at five months. To identify the molecular events crucial to leukemic transformation, we produced several mouse models. We report here that expression of P16INK4A in developing TAL1xLMO1 thymocytes blocks leukemogenesis in the majority of the mice and the leukemias that eventually develop show P16INK4A loss of expression. Events related to the T-cell receptor selection process are thought to be important for leukemic tranformation. We show here that the absence of the pT chain only slightly delays the appearance of TAL1xLMO1-induced T-ALL, which indicates a minor role of the pT chain. We also show that the CD3-mediated signal transduction pathway is essential for this transformation process since the TAL1xLMO1xCD3 deficient mice do not develop T-ALL for up to one year. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. S. Rao, J. O'Neil, C. D. Liberator, J. S. Hardwick, X. Dai, T. Zhang, E. Tyminski, J. Yuan, N. E. Kohl, V. M. Richon, et al. Inhibition of NOTCH Signaling by Gamma Secretase Inhibitor Engages the RB Pathway and Elicits Cell Cycle Exit in T-Cell Acute Lymphoblastic Leukemia Cells Cancer Res., April 1, 2009; 69(7): 3060 - 3068. [Abstract] [Full Text] [PDF]

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