Richardson, S. J., Matthews, C., Catherwood, M. A., Alexander, D. H., Carey, B. S., Farrugia, J., Gardiner, A. C., Mould, S. J., Oscier, D. G., Copplestone, J. A. and Prentice, A. G., 2006. ZAP-70 expression is associated with enhanced ability to respond to migratory and survival signals in B-cell chronic lymphocytic leukemia (B-CLL). Blood, 107 (9), pp. 3584-3592.
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Official URL: http://bloodjournal.hematologylibrary.org/cgi/cont...
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.
|Subjects:||Technology > Medicine and Health|
|Group:||School of Health and Social Care > Centre for Postgraduate Medical Research and Education|
|Deposited By:||INVALID USER|
|Deposited On:||02 Nov 2008 16:08|
|Last Modified:||07 Mar 2013 14:51|
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