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This Article Full Text Full Text (PDF) 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 Barata, J. T. Articles by Boussiotis, V. A. Search for Related Content PubMed PubMed Citation Articles by Barata, J. T. Articles by Boussiotis, V. A. Related Collections Neoplasia Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 September 2001, Vol. 98, No. 5, pp. 1524-1531 NEOPLASIA Interleukin-7 promotes survival and cell cycle progression of T-cell acute lymphoblastic leukemia cells by down-regulating the cyclin-dependent kinase inhibitor p27kip1 Joao T. Barata, Angelo A. Cardoso, Lee M. Nadler, and Vassiliki A. Boussiotis From the Department of Adult Oncology, Dana-Farber Cancer Institute, the Division of Medical Oncology, Brigham and Women's Hospital, Department of Medicine, Harvard Medical School, Boston, MA. In normal T-cell development interleukin-7 (IL-7) functions as an antiapoptotic factor by regulating bcl-2 expression in immature thymocytes and mature T cells. Similar to what occurs in normal immature thymocytes, prevention of spontaneous apoptosis by IL-7 in precursor T-cell acute lymphoblastic leukemia (T-ALL) cells correlates with up-regulation of bcl-2. IL-7 is also implicated in leukemogenesis because IL-7 transgenic mice develop lymphoid malignancies, suggesting that IL-7 may regulate the generation and expansion of malignant cells. This study shows that in the presence of IL-7, T-ALL cells not only up-regulated bcl-2 expression and escaped apoptosis but also progressed in the cell cycle, resulting in sequential induction of cyclin D2 and cyclin A. Down-regulation of p27kip1 was mandatory for IL-7-mediated cell cycle progression and temporally coincided with activation of cyclin-dependent kinase (cdk)4 and cdk2 and hyperphosphorylation of Rb. Strikingly, forced expression of p27kip1 in T-ALL cells not only prevented cell cycle progression but also reversed IL-7-mediated up-regulation of bcl-2 and promotion of viability. These results show for the first time that a causative link between IL-7-mediated proliferation and p27kip1 down-regulation exists in malignant T cells. Moreover, these results suggest that p27kip1 may function as a tumor suppressor gene not only because it is a negative regulator of cell cycle progression but also because it is associated with induction of apoptosis of primary malignant cells. © 2001 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. E. Johnson, N. Shah, A. A. Bajer, and T. W. LeBien IL-7 Activates the Phosphatidylinositol 3-Kinase/AKT Pathway in Normal Human Thymocytes but Not Normal Human B Cell Precursors J. Immunol., June 15, 2008; 180(12): 8109 - 8117. [Abstract] [Full Text] [PDF] S. M. Churchman and F. Ponchel Interleukin-7 in rheumatoid arthritis Rheumatology, June 1, 2008; 47(6): 753 - 759. [Abstract] [Full Text] [PDF] S. R. Jacobs, C. E. Herman, N. J. MacIver, J. A. Wofford, H. L. Wieman, J. J. Hammen, and J. C. 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	Copyright © 2001 by American Society of Hematology         Online ISSN: 1528-0020