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Expression of ZAP-70 is associated with increased B-cell receptor signaling in chronic lymphocytic leukemia

Chen, Liguang, Widhopf, George, Huynh, Lang, Rassenti, Laura, Rai, Kanti R., Weiss, Arthur, Kipps, Thomas J.·2002·Blood
DOI 10.1182/blood-2002-06-1683
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Abstract

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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Cited by

Metadata

Authors
Chen, L., Widhopf, G., Huynh, L., Rassenti, L., Rai, K. R., Weiss, A., & Kipps, T. J.
Affiliations
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.
Venue
Blood
Publisher
American Society of Hematology
Published
2002-12-15
Volume
100
Issue
13
Pages
4609-4614
ISSN
  • 1528-0020
  • 0006-4971
DOI
10.1182/blood-2002-06-1683
Cited by
426
References
0
Language
en

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