Journal
BLOOD
Volume 105, Issue 5, Pages 2036-2041Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2004-05-1715
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Funding
- NCI NIH HHS [R37 CA49870, P01 CA81534] Funding Source: Medline
- NIAID NIH HHS [P01 AI45865] Funding Source: Medline
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Chronic lymphocytic leukemia (CLL) B cells that express unmutated immunoglobulin heavy-chain variable region genes (IgV(H)) generally express ZAP-70, in contrast to normal B cells or most CLL cases with mutated IgV(H). Following IgM ligation, ZAP-70(+) CLL cells had significantly higher levels of phosphorylated p72(Syk), BLNK, and phospholipase-Cgamma (PLCgamma) and had greater [Ca2+](j) flux than did ZAP-70-negative CLL cases, including unusual ZAP-70-negative cases with unmutated IgV(H). IgM ligation of ZAP-70-negative CLL B cells infected with an adenovirus vector encoding ZAP-70 induced significantly greater levels of phosphorylated p72(Syk), BLNK, and PLC-gamma and had greater[Ca2+](j) 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 IgV(H). (C) 2005 by The American Society of Hematology.
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