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Blood, 15 December 2007, Vol. 110, No. 13, pp. 4406-4416. Prepublished online as a Blood First Edition Paper on September 10, 2007; DOI 10.1182/blood-2006-11-059501. This Article Full Text (PDF) Supplemental Figure All Versions of this Article: blood-2006-11-059501v1 110/13/4406    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 Despouy, G. Articles by Stern, M. H. Search for Related Content PubMed PubMed Citation Articles by Despouy, G. Articles by Stern, M. H. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted November 29, 2006 Accepted August 12, 2007 The TCL1 oncoprotein inhibits activation-induced cell death by impairing PKC and ERK pathways Gilles Despouy, Marjorie Joiner, Emilie Le Toriellec, Robert Weil, and Marc Henri Stern* Centre de Recherche, Institut Curie, Paris, France INSERM U830, Paris, France CNRS URA 2582, Institut Pasteur, Paris, France * Corresponding author; email: marc-henri.stern{at}curie.fr. The TCL1/MTCP1 oncogenes were identified on the basis of their involvement in T-cell prolymphocytic leukemia (T-PLL). TCL1 and MTCP1 proteins directly interact with AKT and modulate the AKT signal-transduction pathway, but the relevance of this mechanism in leukemogenesis remains unclear. We investigate the biological functions of TCL1 in the T-cell lineage using various cell lines, and primary malignant and normal lymphocytes. In the Jurkat cell line, expression of TCL1 had no effect in unstimulated cells, whereas it abrogated activation-induced cell death (AICD). These cellular effects were concomitant with a major inhibition by TCL1 of PKC and ERK pathways. Secondly, the TCL1-driven T-cell leukemia cell line SUP-T11 was shown to have impaired PKC and ERK phosphorylation upon stimulation, which were restored by TCL1 inhibition using RNA interference. Finally, defects in these pathways were also observed in primary malignant (T-PLL) and transduced normal T lymphocytes expressing TCL1. Altogether, our data demonstrated that TCL1 inhibits AICD in T-cells by blocking PKC and ERK activation, upon cellular activation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. Herling, K. A. Patel, N. Weit, N. Lilienthal, M. Hallek, M. J. Keating, and D. Jones High TCL1 levels are a marker of B-cell receptor pathway responsiveness and adverse outcome in chronic lymphocytic leukemia Blood, November 19, 2009; 114(21): 4675 - 4686. [Abstract] [Full Text] [PDF] D. Nowak, E. Le Toriellec, M.-H. Stern, N. Kawamata, T. Akagi, M. J. Dyer, W.-K. Hofmann, S. Ogawa, and H. P. Koeffler Molecular allelokaryotyping of T-cell prolymphocytic leukemia cells with high density single nucleotide polymorphism arrays identifies novel common genomic lesions and acquired uniparental disomy Haematologica, April 1, 2009; 94(4): 518 - 527. [Abstract] [Full Text] [PDF] S. C. Morley, K. S. Weber, H. Kao, and P. M. Allen Protein Kinase C-{theta} Is Required for Efficient Positive Selection J. Immunol., October 1, 2008; 181(7): 4696 - 4708. [Abstract] [Full Text] [PDF] E. Le Toriellec, G. Despouy, G. Pierron, N. Gaye, M. Joiner, D. Bellanger, A. Vincent-Salomon, and M.-H. Stern Haploinsufficiency of CDKN1B contributes to leukemogenesis in T-cell prolymphocytic leukemia Blood, February 15, 2008; 111(4): 2321 - 2328. [Abstract] [Full Text] [PDF]

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