ZAP-70 protein expression and CD38 positivity in B-cell chronic lymphocytic leukemia.
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.


CONCLUSIONS
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.
Ertault-Daneshpouy
Marjan
M
Institut Universitaire d'Hématologie, Hopital St Louis, 75010 Paris, France.
Noguera
Maria Elena
ME
Gisselbrecht
Christian
C
Haddad
Albert
A
Brice
Pauline
P
Marolleau
Jean-Pierre
JP
Soulier
Jean
J
Mounier
Nicolas
N
D051997:ADP-ribosyl Cyclase 1 / Q000378:metabolism*; D016175:B-Lymphocyte Subsets / Q000145:classification / Q000378:metabolism*; D015415:Biomarkers / Q000097:blood; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000145:classification / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000378:metabolism*
D015415:Biomarkers; D008562:Membrane Glycoproteins; D051746:ZAP-70 Protein-Tyrosine Kinase; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1