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Blood, 1 February 2007, Vol. 109, No. 3, pp. 1193-1201. Prepublished online as a Blood First Edition Paper on September 26, 2006; DOI 10.1182/blood-2006-03-012021. This Article Full Text (PDF) Supplemental Table All Versions of this Article: blood-2006-03-012021v1 109/3/1193    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 Abrams, S. T Articles by Slupsky, J. R Search for Related Content PubMed PubMed Citation Articles by Abrams, S. T Articles by Slupsky, J. R Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted March 22, 2006 Accepted September 18, 2006 B cell receptor signalling in chronic lymphocytic leukaemia cells is regulated by overexpressed active protein kinase CII Simon T Abrams, Tasneem Lakum, Ke Lin, Gemma M Jones, Andrew T Treweeke, Mosavar Farahani, Mair Hughes, Mirko Zuzel, and Joseph R Slupsky* Department of Haematology, University of Liverpool, Liverpool, United Kingdom * Corresponding author; email: jslupsky{at}liverpool.ac.uk. Signals through the B-cell antigen receptor (BCR) are important for survival of chronic lymphocytic leukaemia (CLL) cells. Therefore, factors that influence these signals have important pathophysiological roles in this disease. One key mediator of BCR signalling is protein kinase C (PKC), which regulates activation of I-B kinases and deactivation of Bruton's tyrosine kinase within the signalling pathways initiated by BCR engagement. The present study demonstrates that overexpression of the PKCII isoform is a feature of CLL cells, and that activity of this enzyme strongly correlates with CLL-cell response to BCR engagement. Thus, intracellular Ca2+ release and increases in cell survival following BCR crosslinking were significantly greater in CLL cases with low levels, than in cases with high levels of active PKCII. Furthermore, BCR-induced Ca2+ fluxes could be restored in CLL cases with high levels of active PKCII by pre-treating the cells with the PKC-specific inhibitor LY379196. Conversely, BCR-mediated intracellular Ca2+ release could be inhibited in CLL cells with low levels of active PKCII by pre-treatment with the PKC agonist bryostatin. Taken together, these results demonstrate that overexpressed active PKCII plays a role in the regulation and outcome of BCR signals that can be important for the progression of CLL. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Protein kinase C inhibitor enzastaurin induces in vitro and in vivo antitumor activity in Waldenström macroglobulinemia Anne-Sophie Moreau, Xiaoying Jia, Hai T. Ngo, Xavier Leleu, Garrett O'Sullivan, Yazan Alsayed, Alexey Leontovich, Klaus Podar, Jeffrey Kutok, John Daley, Suzan Lazo-Kallanian, Evdoxia Hatjiharissi, Marc S. Raab, Lian Xu, Steven P. Treon, Teru Hideshima, Kenneth C. Anderson, and Irene M. Ghobrial Blood 2007 109: 4964-4972. [Abstract] [Full Text] [PDF] This article has been cited by other articles: A.-S. Moreau, X. Jia, H. T. Ngo, X. Leleu, G. O'Sullivan, Y. Alsayed, A. Leontovich, K. Podar, J. Kutok, J. Daley, et al. Protein kinase C inhibitor enzastaurin induces in vitro and in vivo antitumor activity in Waldenstrom macroglobulinemia Blood, June 1, 2007; 109(11): 4964 - 4972. [Abstract] [Full Text] [PDF]

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