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Blood, 12 March 2009, Vol. 113, No. 11, pp. 2508-2516. Prepublished online as a Blood First Edition Paper on November 3, 2008; DOI 10.1182/blood-2008-05-158618. This Article Full Text Full Text (PDF) Supplemental Figure All Versions of this Article: blood-2008-05-158618v1 113/11/2508    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 Young, R. M. Articles by Refaeli, Y. Search for Related Content PubMed PubMed Citation Articles by Young, R. M. Articles by Refaeli, Y. Related Collections Lymphoid Neoplasia Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  LYMPHOID NEOPLASIA Mouse models of non-Hodgkin lymphoma reveal Syk as an important therapeutic target Ryan M. Young1,2, Ian R. Hardy2, Raedun L. Clarke2, Nicolai Lundy1, Polly Pine3, Brian C. Turner1, Terry A. Potter2, and Yosef Refaeli1,2,4 1 Department of Pediatrics, Program in Cell Biology, National Jewish Medical and Research Center, Denver, CO; 2 Department of Immunology, University of Colorado Denver Health and Sciences Center, Aurora; 3 Rigel Pharmaceuticals, South San Francisco, CA; and 4 University of Colorado Cancer Center, Aurora We have generated mouse models of non-Hodgkin lymphoma (NHL) that rely on the cooperation between MYC overexpression and B-cell antigen receptor (BCR) signaling for the initiation and maintenance of B-cell lymphomas. Using these mouse models of NHL, we have focused on the identification of BCR-derived signal effectors that are important for the maintenance of NHL tumors. In the present study, we concentrate on Spleen tyrosine kinase (Syk), a nonreceptor tyrosine kinase required to transduce BCR-dependent signals. Using a genetic approach, we showed that Syk expression is required for the survival of murine NHL-like tumors in vitro and that tumor cells deficient in Syk fail to expand in vivo. In addition, a pharmacologic inhibitor of Syk was able to induce apoptosis of transformed B cells in vitro and led to tumor regression in vivo. Finally, we show that genetic or pharmacologic inhibition of Syk activity in human NHL cell lines are generally consistent with results found in the mouse models, suggesting that targeting Syk may be a viable therapeutic strategy. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Syk to death P. Leif Bergsagel Blood 2009 113: 2371. [Full Text] [PDF] This article has been cited by other articles: M. P. Quiroga, K. Balakrishnan, A. V. Kurtova, M. Sivina, M. J. Keating, W. G. Wierda, V. Gandhi, and J. A. Burger B-cell antigen receptor signaling enhances chronic lymphocytic leukemia cell migration and survival: specific targeting with a novel spleen tyrosine kinase inhibitor, R406 Blood, July 30, 2009; 114(5): 1029 - 1037. [Abstract] [Full Text] [PDF] S.-W. Kim, D. Rai, M. R. McKeller, and R. C. T. Aguiar Rational combined targeting of phosphodiesterase 4B and SYK in DLBCL Blood, June 11, 2009; 113(24): 6153 - 6160. [Abstract] [Full Text] [PDF] P. L. Bergsagel Syk to death Blood, March 12, 2009; 113(11): 2371 - 2371. [Full Text] [PDF]

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