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Prepublished online as a Blood First Edition Paper on August 8, 2002; DOI 10.1182/blood-2002-06-1683.
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Blood, 15 December 2002, Vol. 100, No. 13, pp. 4609-4614
NEOPLASIA
Expression of ZAP-70 is associated with increased B-cell receptor
signaling in chronic lymphocytic leukemia
Liguang Chen,
George Widhopf,
Lang Huynh,
Laura Rassenti,
Kanti R. Rai,
Arthur Weiss, and
Thomas J. Kipps
From the Division of Hematology/Oncology, Department of
Medicine, University of California, San Diego for the CLL Research
Consortium, San Diego, CA; Long Island Jewish Hospital, New
York, NY; and the Department of Medicine, Howard Hughes Medical
Institute, University of California, San Francisco.
We examined isolated leukemia B cells of patients with chronic
lymphocytic leukemia (CLL) for expression of zeta-associated protein 70 (ZAP-70). CLL B cells that have nonmutated
immunoglobulin variable region genes (V genes) expressed levels
of ZAP-70 protein that were comparable to those expressed by normal
blood T cells. In contrast, CLL B cells that had mutated immunoglobulin
variable V genes, or that had low-level expression of CD38,
generally did not express detectable amounts of ZAP-70 protein.
Leukemia cells from identical twins with CLL were found discordant for
expression of ZAP-70, suggesting that B-cell expression of ZAP-70 is
not genetically predetermined. Ligation of the B-cell receptor (BCR) complex on CLL cells that expressed ZAP-70 induced significantly greater tyrosine phosphorylation of cytosolic proteins, including p72Syk, than did similar stimulation of CLL cells that did
not express ZAP-70. Also, exceptional cases of CLL cells that expressed
mutated immunoglobulin V genes and ZAP-70 also experienced higher
levels tyrosine phosphorylation of such cytosolic proteins following BCR ligation. Following BCR ligation, ZAP-70 underwent tyrosine phosphorylation and became associated with surface immunoglobulin and
CD79b, arguing for the involvement of ZAP-70 in BCR
signaling. These data indicate that expression of ZAP-70 is associated
with enhanced signal transduction via the BCR complex, which may
contribute to the more aggressive clinical course associated with CLL
cells that express nonmutated immunoglobulin receptors.
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
|
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August 1, 2006;
108(3):
853 - 861.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P.-A. Deglesne, N. Chevallier, R. Letestu, F. Baran-Marszak, T. Beitar, C. Salanoubat, L. Sanhes, J. Nataf, C. Roger, N. Varin-Blank, et al.
Survival response to B-cell receptor ligation is restricted to progressive chronic lymphocytic leukemia cells irrespective of zap70 expression.
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July 15, 2006;
66(14):
7158 - 7166.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. J. Richardson, C. Matthews, M. A. Catherwood, H. D. Alexander, B. S. Carey, J. Farrugia, A. Gardiner, S. Mould, D. Oscier, J. A. Copplestone, et al.
ZAP-70 expression is associated with enhanced ability to respond to migratory and survival signals in B-cell chronic lymphocytic leukemia (B-CLL)
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May 1, 2006;
107(9):
3584 - 3592.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. H. Khan, S. Mendoza, P. Rhyne, M. Ziman, J. Tuscano, D. Eisinger, H.-J. Kung, and P. A. Luciw
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5(4):
758 - 768.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Kienle, A. Benner, A. Krober, D. Winkler, D. Mertens, A. Buhler, T. Seiler, U. Jager, P. Lichter, H. Dohner, et al.
Distinct gene expression patterns in chronic lymphocytic leukemia defined by usage of specific VH genes
Blood,
March 1, 2006;
107(5):
2090 - 2093.
[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]
|
|
|
|
|
|
|
M. Crespo, N. Villamor, E. Gine, A. Muntanola, D. Colomer, T. Marafioti, M. Jones, M. Camos, E. Campo, E. Montserrat, et al.
ZAP-70 Expression in Normal Pro/Pre B Cells, Mature B Cells, and in B-Cell Acute Lymphoblastic Leukemia
Clin. Cancer Res.,
February 1, 2006;
12(3):
726 - 734.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Chiaretti, A. Guarini, M. S. De Propris, S. Tavolaro, S. Intoppa, A. Vitale, S. Iacobelli, L. Elia, C. Ariola, J. Ritz, et al.
ZAP-70 expression in acute lymphoblastic leukemia: association with the E2A/PBX1 rearrangement and the pre-B stage of differentiation and prognostic implications
Blood,
January 1, 2006;
107(1):
197 - 204.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. J. Allsup, A. S. Kamiguti, K. Lin, P. D. Sherrington, Z. Matrai, J. R. Slupsky, J. C. Cawley, and M. Zuzel
B-Cell Receptor Translocation to Lipid Rafts and Associated Signaling Differ between Prognostically Important Subgroups of Chronic Lymphocytic Leukemia
Cancer Res.,
August 15, 2005;
65(16):
7328 - 7337.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. V. Abruzzo, J. Wang, M. Kapoor, L. J. Medeiros, M. J. Keating, W. E. Highsmith, L. L. Barron, C. C. Cromwell, and K. R. Coombes
Biological Validation of Differentially Expressed Genes in Chronic Lymphocytic Leukemia Identified by Applying Multiple Statistical Methods to Oligonucleotide Microarrays
J. Mol. Diagn.,
August 1, 2005;
7(3):
337 - 345.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Oppezzo, Y. Vasconcelos, C. Settegrana, D. Jeannel, F. Vuillier, M. Legarff-Tavernier, E. Y. Kimura, S. Bechet, G. Dumas, M. Brissard, et al.
The LPL/ADAM29 expression ratio is a novel prognosis indicator in chronic lymphocytic leukemia
Blood,
July 15, 2005;
106(2):
650 - 657.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Falt, M. Merup, G. Tobin, U. Thunberg, G. Gahrton, R. Rosenquist, and A. Wennborg
Distinctive gene expression pattern in VH3-21 utilizing B-cell chronic lymphocytic leukemia
Blood,
July 15, 2005;
106(2):
681 - 689.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Petlickovski, L. Laurenti, X. Li, S. Marietti, P. Chiusolo, S. Sica, G. Leone, and D. G. Efremov
Sustained signaling through the B-cell receptor induces Mcl-1 and promotes survival of chronic lymphocytic leukemia B cells
Blood,
June 15, 2005;
105(12):
4820 - 4827.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Raval, D. M. Lucas, J. J. Matkovic, K. L. Bennett, S. Liyanarachchi, D. C. Young, L. Rassenti, T. J. Kipps, M. R. Grever, J. C. Byrd, et al.
TWIST2 Demonstrates Differential Methylation in Immunoglobulin Variable Heavy Chain Mutated and Unmutated Chronic Lymphocytic Leukemia
J. Clin. Oncol.,
June 10, 2005;
23(17):
3877 - 3885.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. L. Kienle, C. Korz, B. Hosch, A. Benner, D. Mertens, A. Habermann, A. Krober, U. Jager, P. Lichter, H. Dohner, et al.
Evidence for Distinct Pathomechanisms in Genetic Subgroups of Chronic Lymphocytic Leukemia Revealed by Quantitative Expression Analysis of Cell Cycle, Activation, and Apoptosis-Associated Genes
J. Clin. Oncol.,
June 1, 2005;
23(16):
3780 - 3792.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Nedellec, Y. Renaudineau, A. Bordron, C. Berthou, N. Porakishvili, P. M. Lydyard, J.-O. Pers, and P. Youinou
B Cell Response to Surface IgM Cross-Linking Identifies Different Prognostic Groups of B-Chronic Lymphocytic Leukemia Patients
J. Immunol.,
March 15, 2005;
174(6):
3749 - 3756.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Chen, J. Apgar, L. Huynh, F. Dicker, T. Giago-McGahan, L. Rassenti, A. Weiss, and T. J. Kipps
ZAP-70 directly enhances IgM signaling in chronic lymphocytic leukemia
Blood,
March 1, 2005;
105(5):
2036 - 2041.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
