ZAP-70 Protein Expression and CD38 Positivity in B-cell Chronic Lymphocytic Leukemia.

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ZAP-70 Protein Expression and CD38 Positivity in B-cell Chronic Lymphocytic

Leukemia.

Marjan Ertault-Daneshpouy, Elena Noguera, Christian Gisselbrecht, Albert

Haddad, ine Brice, Jean-Pierre Marolleau, Soulier, and Nicolas Mounier

Clin Adv Hematol Oncol, January 1, 2008; 6(1): 55-63.

Institut Universitaire d?Hématologie, Hopital St Louis, 75010 Paris, France.

BACKGROUND: The clinical course, disease progression, and survival of B-cell

chronic lymphocytic leukemia (B-CLL) have been correlated with immunoglobulin

heavy-chain variable region mutation status. The biologic parameters 70-kDa

zeta-associated protein (ZAP-70) and CD38 expression are easier and faster

surrogate markers for mutational status. OBJECTIVE: To assess retrospectively

ZAP-70 expression in B-CLL cells using flow cytometry and examine its

relationship with CD38 expression and the median time from diagnosis to initial

therapy. METHODS: Ninety-four unselected patients who had their follow-up in the

outpatient clinic from 2004 to 2005 were reviewed for immunophenotyping ZAP-70

and CD38 expression. Direct immunolabeling with clone 2E3.2, isotype IgG2a,

enabled easy quantification of ZAP-70 by flow cytometry in association with CD38

expression; in addition, the mean fluorescence intensity ratio (MFIR) of

CD19+CD5+ B-CLL cells compared to an isotype control monoclonal antibody was

determined. RESULTS: ZAP-70 expression levels in B-CLL cells varied widely

(0.3-99%). The median time to therapy was significantly shorter for the 54

patients with 20% or more ZAP-70+ cells (30 months) than for the 40 patients

with less than 20% ZAP-70+ cells (median time to treatment not reached). The

optimal MFIR for classifying patients as ZAP-70+ was 2. Thirty-two patients had

a threshold of ZAP-70+CD38+ greater than 30%, with a median time from diagnosis

to treatment of 19 months. Regardless of CD38 expression level, CD38 and ZAP-70

expressions were significantly associated. The median interval from diagnosis to

initial therapy was 16.2 months for ZAP-70+CD38+ patients, 60 months for

ZAP-70+CD38- or ZAP-70-CD38+ patients, and had not yet been reached for

ZAP-70-CD38- patients. CONCLUSION: The association of ZAP-70+CD19+CD5+ B-CLL

cells and percentage of CD38+CD19+CD5+ B-CLL cells evaluated by flow cytometry

provide reliable methods that could be introduced into a routine diagnostic

B-CLL panel to predict outcome.

PMID: 18322442