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ZAP-70 directly enhances IgM signaling in chronic lymphocytic leukemia
Abstract
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-Cγ (PLCγ) 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 PLCγ 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.
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“ZAP70 is expressed in human CLL, is a negative prognostic factor in this disease(2, 3), and regulates BCR signaling in CLL cells(4-6).”
From Involvement of RhoH GTPase in the development of B-cell chronic lymphocytic leukemia (2010) · cites this paper as [5]
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Self-citationB cell receptor signaling in chronic lymphocytic leukemia
Burger, J. A., & Chiorazzi, N. (2013) · Trends in Immunology · doi:10.1016/j.it.2013.07.002 · Cited by 327
Gobessi, S., Laurenti, L., Longo, P. G., Carsetti, L., Berno, V, Sica, S., Leone, G., & Efremov, D. G. (2009) · Leukemia · doi:10.1038/leu.2008.346 · Cited by 200
Metadata
- Authors
- Chen, L., Apgar, J., Huynh, L., Dicker, F., Giago-McGahan, T., Rassenti, L., Weiss, A., & Kipps, T. J.
- Affiliations
- 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.
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2005-03-01
- Volume
- 105
- Issue
- 5
- Pages
- 2036-2041
- ISSN
- 0006-4971
- 1528-0020
- Cited by
- 202
- References
- 2
- Language
- en
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