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Correlation between ZAP‐70, phospho‐ZAP‐70, and phospho‐Syk expression in leukemic cells from patients with CLL
Author(s) -
Kaplan David,
Meyerson Howard J.,
Li Xiaofeng,
Drasny Carly,
Liu Fangfang,
Costaldi Mark,
Barr Paul,
Lazarus Hillard M.
Publication year - 2010
Publication title -
cytometry part b: clinical cytometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.646
H-Index - 61
eISSN - 1552-4957
pISSN - 1552-4949
DOI - 10.1002/cyto.b.20506
Subject(s) - syk , phosphorylation , chronic lymphocytic leukemia , cancer research , immunophenotyping , proximity ligation assay , signal transduction , leukemia , biology , antigen , receptor , immunology , microbiology and biotechnology , tyrosine kinase , biochemistry
For patients with chronic lymphocytic leukemia (CLL), expression of ZAP‐70 in the leukemic cells is an indicator of poor prognosis. However, the mechanism that accounts for this effect is not known. ZAP‐70 expression has previously been associated with increased B cell antigen receptor signaling upon surface immunoglobulin ligation in vitro as shown by ZAP‐70 and Syk phosphorylation. This finding has led to the suggestion that a more aggressive clinical course is correlated with B cell antigen receptor signaling. Using high resolution immunophenotyping to analyze CLL cells ex vivo (without stimulation in vitro ), we have demonstrated CLL cells from all patients express some ZAP‐70 and that increased expression of ZAP‐70 is correlated with decreased levels of phosphorylated ZAP‐70 and phosphorylated Syk measured directly ex vivo . Conversely, high levels of phosphorylated ZAP‐70 and phosphorylated Syk are found only in samples with low levels of ZAP‐70 expression, and Syk and ZAP‐70 phosphorylation appear to be mostly independent of each other. Additionally, Syk phosphorylation is directly correlated with levels of p21 cip1 , a cell cycle inhibitor and a p53 target. Together these findings suggest that lower levels of p21 cip1 and/or a defect in p53 activity may account in part for the more aggressive disease course in patients with high levels of ZAP‐70 rather than enhanced B cell antigen receptor signaling as has been previously hypothesized. © 2009 Clinical Cytometry Society