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Blood, 1 March 2005, Vol. 105, No. 5, pp. 2036-2041. Prepublished online as a Blood First Edition Paper on October 28, 2004; DOI 10.1182/blood-2004-05-1715. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-05-1715v1 105/5/2036    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 Chen, L. Articles by Kipps, T. J. Search for Related Content PubMed PubMed Citation Articles by Chen, L. Articles by Kipps, T. J. Related Collections Immunobiology Neoplasia Gene Therapy Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY ZAP-70 directly enhances IgM signaling in chronic lymphocytic leukemia Liguang Chen, John Apgar, Lang Huynh, Frank Dicker, Teresa Giago-McGahan, Laura Rassenti, Arthur Weiss, and Thomas J. Kipps From the Division of Hematology/Oncology, Department of Medicine, University of California, San Diego; Department of Cell Signaling Research, BD PharMingen; Department of Medicine, Howard Hughes Medical Institute, University of California, San Francisco; and the Chronic Lymphocytic Leukemia (CLL) Research Consortium, University of California, San Diego. Chronic lymphocytic leukemia (CLL) B cells that express unmutated immunoglobulin heavy-chain variable region genes (IgVH) generally express ZAP-70, in contrast to normal B cells or most CLL cases with mutated IgVH. Following IgM ligation, ZAP-70+ CLL cells had significantly higher levels of phosphorylated p72Syk, BLNK, and phospholipase-C (PLC) and had greater[Ca2+]i flux than did ZAP-70–negative CLL cases, including unusual ZAP-70–negative cases with unmutated IgVH. IgM ligation of ZAP-70–negative CLL B cells infected with an adenovirus vector encoding ZAP-70 induced significantly greater levels of phosphorylated p72Syk, BLNK, and PLC and had greater[Ca2+]i flux than did similarly stimulated, noninfected CLL cells or CLL cells infected with a control adenovirus vector. We conclude that expression of ZAP-70 in CLL allows for more effective IgM signaling in CLL B cells, a feature that could contribute to the relatively aggressive clinical behavior generally associated with CLL cells that express unmutated IgVH. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? 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Luciw Multiplex Analysis of Intracellular Signaling Pathways in Lymphoid Cells by Microbead Suspension Arrays Mol. Cell. Proteomics, April 1, 2006; 5(4): 758 - 768. [Abstract] [Full Text] [PDF] K. N. Potter, C. I. Mockridge, L. Neville, I. Wheatley, M. Schenk, J. Orchard, A. S. Duncombe, G. Packham, and F. K. Stevenson Structural and Functional Features of the B-Cell Receptor in IgG-Positive Chronic Lymphocytic Leukemia. Clin. Cancer Res., March 15, 2006; 12(6): 1672 - 1679. [Abstract] [Full Text] [PDF] A. Krober, J. Bloehdorn, S. Hafner, A. Buhler, T. Seiler, D. Kienle, D. Winkler, M. Bangerter, R. F. Schlenk, A. Benner, et al. Additional Genetic High-Risk Features Such As 11q Deletion, 17p Deletion, and V3-21 Usage Characterize Discordance of ZAP-70 and VH Mutation Status in Chronic Lymphocytic Leukemia J. Clin. Oncol., February 20, 2006; 24(6): 969 - 975. [Abstract] [Full Text] [PDF] S. Chiaretti, A. Guarini, M. S. De Propris, S. Tavolaro, S. Intoppa, A. Vitale, S. Iacobelli, L. 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