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Blood, 1 March 2004, Vol. 103, No. 5, pp. 1891-1900. Prepublished online as a Blood First Edition Paper on November 13, 2003; DOI 10.1182/blood-2002-12-3861. This Article Full Text (PDF) All Versions of this Article: 2002-12-3861v1 103/5/1891    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 Barata, J. T Articles by Cardoso, A. A Search for Related Content PubMed PubMed Citation Articles by Barata, J. T Articles by Cardoso, A. A Social Bookmarking                   What's this? Submitted December 30, 2002 Accepted October 29, 2003 An IL-7-dependent human leukemia T-cell line as a valuable tool for drug discovery in T-ALL Joao T Barata, Vassiliki A Boussiotis, Jose A Yunes, Adolfo A Ferrando, Lisa A Moreau, J P Veiga, Stephen E Sallan, A T Look, Lee M Nadler, and Angelo A Cardoso* Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA Unit of Tumor Biology, Institute of Molecular Medicine, Lisbon, Portugal * Corresponding author; email: cardoso{at}mbcrr.harvard.edu. The specific targeting of critical signaling molecules may provide efficient therapies for T-cell acute lymphoblastic leukemia (T-ALL). However target identification and drug development are limited by insufficient numbers of primary T-ALL cells and by their high rate of spontaneous apoptosis. We established a human IL-7-dependent T-ALL cell line - TAIL7 - that maintains several biological and signaling properties of its parental leukemia cells. TAIL7 are pre-T ALL cells that proliferate in response to IL-7 and IL-4. IL-7-stimulation of TAIL7 cells prevents spontaneous in vitro apoptosis, induces cell activation and cell cycle progression. The signaling events triggered by IL-7 include downregulation of p27kip1 and hyperphosphorylation of Rb. Stimulation of TAIL7 cells by IL-7 leads to phosphorylation of JAK3, STAT5, Akt/PKB and Erk1/2. Importantly, specific blockade of Jak3 by its inhibitor WHI-P131 abrogates the IL-7-mediated proliferation and survival of TAIL7 cells, suggesting that activation of Jak3 is critical for IL-7 responsiveness by these cells. Since TAIL7 cells seem to be a biological surrogate for primary leukemia T-cells, this cell line constitutes a valuable tool for the study of the signaling pathways implicated in T-ALL. Exploitation of this cell line should allow the identification of molecular targets and promote the rational design and validation of anti-leukemia signaling-inhibitors. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: E. G. Jeong, M. S. Kim, H. K. Nam, C. K. Min, S. Lee, Y. J. Chung, N. J. Yoo, and S. H. Lee Somatic Mutations of JAK1 and JAK3 in Acute Leukemias and Solid Cancers Clin. Cancer Res., June 15, 2008; 14(12): 3716 - 3721. [Abstract] [Full Text] [PDF] J. A. Wofford, H. L. Wieman, S. R. Jacobs, Y. Zhao, and J. C. Rathmell IL-7 promotes Glut1 trafficking and glucose uptake via STAT5-mediated activation of Akt to support T-cell survival Blood, February 15, 2008; 111(4): 2101 - 2111. [Abstract] [Full Text] [PDF] S. C. R. Santos, I. Vala, C. Miguel, J. T. Barata, P. Garcao, P. Agostinho, M. Mendes, A. V. Coelho, A. Calado, C. R. Oliveira, et al. Expression and Subcellular Localization of a Novel Nuclear Acetylcholinesterase Protein J. Biol. Chem., August 31, 2007; 282(35): 25597 - 25603. [Abstract] [Full Text] [PDF] A. Acacia de Sa Pinheiro, A. Morrot, S. Chakravarty, M. Overstreet, J. H. Bream, P. M. Irusta, and F. Zavala IL-4 induces a wide-spectrum intracellular signaling cascade in CD8+ T cells J. Leukoc. Biol., April 1, 2007; 81(4): 1102 - 1110. [Abstract] [Full Text] [PDF] J. T. Barata, A. Silva, J. G. Brandao, L. M. Nadler, A. A. Cardoso, and V. A. Boussiotis Activation of PI3K Is Indispensable for Interleukin 7-mediated Viability, Proliferation, Glucose Use, and Growth of T Cell Acute Lymphoblastic Leukemia Cells J. Exp. Med., September 7, 2004; 200(5): 659 - 669. [Abstract] [Full Text] [PDF]

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