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Blood, 1 May 2006, Vol. 107, No. 9, pp. 3584-3592. Prepublished online as a Blood First Edition Paper on December 6, 2005; DOI 10.1182/blood-2005-04-1718. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-04-1718v1 107/9/3584    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 Richardson, S. J. Articles by Prentice, A. G. Search for Related Content PubMed PubMed Citation Articles by Richardson, S. J. Articles by Prentice, A. G. Related Collections Immunobiology Neoplasia Cell Adhesion and Motility Signal Transduction Gene Expression Chemokines, Cytokines, and Interleukins Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY ZAP-70 expression is associated with enhanced ability to respond to migratory and survival signals in B-cell chronic lymphocytic leukemia (B-CLL) Sarah J. Richardson, Christine Matthews, Mark A. Catherwood, H. Denis Alexander, B. Sean Carey, Joanna Farrugia, Anne Gardiner, Sarah Mould, David Oscier, J. Adrian Copplestone, and Archibald G. Prentice From the Department of Haematology, Derriford Hospital, Plymouth, United Kingdom; Department of Haematology, Belfast City Hospital, Belfast, Northern Ireland, United Kingdom; Department of Haematology, Royal Bournemouth Hospital, Bournemouth, United Kingdom; and Department of Haematology, Royal Free and University College Medical School, London, United Kingdom. Molecular markers like IgVH mutational status, chromosomal abnormalities, and CD38 and ZAP-70 expression have prognostic value in B-cell chronic lymphocytic leukemia (B-CLL). These may be pathogenetic because of the coincidental expression of ZAP-70 and increased B-cell receptor (BCR) signaling and the signaling function of CD38 in CLL. This study shows that ZAP-70+ CLL B cells respond in vitro more readily than ZAP-70– CLL and normal B cells to chemokine migratory signals through enhanced surface CCR7 expression (P = .009; P < .001) and increased responsiveness to its ligands CCL19 and CCL21, demonstrated by F-actin polymerization (P < .05) and cellular migration (P < .01). In addition, ZAP-70+ CLL cells exhibit sustained ERK phosphorylation/activation following stimulation with CXCL12 (SDF1-, a survival factor produced by stromal cells) compared with ZAP-70– cells (P = .004). Following coculture with nurse-like cells, the survival of ZAP-70+ but not ZAP-70– CLL cells is significantly enhanced by the addition of CXCL12 (P < .05), an effect that is partially blocked by the MEK inhibitor PD98059. These advantageous migratory and survival responses may promote easier access to and greater proliferation in pseudo-germinal centers and explain in part the more progressive nature of ZAP-70+ disease. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. Deaglio and F. Malavasi Chronic lymphocytic leukemia microenvironment: shifting the balance from apoptosis to proliferation Haematologica, June 1, 2009; 94(6): 752 - 756. [Full Text] [PDF] B. Stamatopoulos, B. Haibe-Kains, C. Equeter, N. Meuleman, A. Soree, C. De Bruyn, D. Hanosset, D. Bron, P. Martiat, and L. 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