{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T08:31:18Z","timestamp":1780043478927,"version":"3.53.1"},"reference-count":32,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2009,12,14]],"date-time":"2009-12-14T00:00:00Z","timestamp":1260748800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cytometry Part B Clinical"],"published-print":{"date-parts":[[2010,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>For patients with chronic lymphocytic leukemia (CLL), expression of ZAP\u201070 in the leukemic cells is an indicator of poor prognosis. However, the mechanism that accounts for this effect is not known. ZAP\u201070 expression has previously been associated with increased B cell antigen receptor signaling upon surface immunoglobulin ligation <jats:italic>in vitro<\/jats:italic> as shown by ZAP\u201070 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 <jats:italic>ex vivo<\/jats:italic> (without stimulation <jats:italic>in vitro<\/jats:italic>), we have demonstrated CLL cells from all patients express some ZAP\u201070 and that increased expression of ZAP\u201070 is correlated with decreased levels of phosphorylated ZAP\u201070 and phosphorylated Syk measured directly <jats:italic>ex vivo<\/jats:italic>. Conversely, high levels of phosphorylated ZAP\u201070 and phosphorylated Syk are found only in samples with low levels of ZAP\u201070 expression, and Syk and ZAP\u201070 phosphorylation appear to be mostly independent of each other. Additionally, Syk phosphorylation is directly correlated with levels of p21<jats:sup>cip1<\/jats:sup>, a cell cycle inhibitor and a p53 target. Together these findings suggest that lower levels of p21<jats:sup>cip1<\/jats:sup> and\/or a defect in p53 activity may account in part for the more aggressive disease course in patients with high levels of ZAP\u201070 rather than enhanced B cell antigen receptor signaling as has been previously hypothesized. \u00a9 2009 Clinical Cytometry Society<\/jats:p>","DOI":"10.1002\/cyto.b.20506","type":"journal-article","created":{"date-parts":[[2009,12,14]],"date-time":"2009-12-14T21:10:04Z","timestamp":1260825004000},"page":"115-122","source":"Crossref","is-referenced-by-count":13,"title":["Correlation between ZAP\u201070, phospho\u2010ZAP\u201070, and phospho\u2010Syk expression in leukemic cells from patients with CLL"],"prefix":"10.1002","volume":"78B","author":[{"given":"David","family":"Kaplan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Howard 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