ZAP-70 expression is a prognostic factor in chronic lymphocytic leukemia.
B-cell chronic lymphocytic leukemia (B-CLL) is a heterogenous disease with a highly variable clinical course. Recent studies have shown that expression of the protein tyrosine kinase ZAP-70 may serve as a prognostic marker in B-CLL. Employing a semiquantitative RT-PCR assay, we examined purified leukemia B cells of 39 CLL patients for the expression of ZAP-70 mRNA transcripts. Significant ZAP-70 mRNA levels exceeding those found in control samples with 5% T cells were detected in 36% of the CLL cases. Patients in the ZAP-70 positive cohort were characterized by an unfavorable clinical course with a significantly shorter progression-free survival as compared to the ZAP-70-negative patients (64%). These results were confirmed by flow-cytometric analysis of the ZAP-70 protein, and expanded to a larger patient cohort (n=67). A combined statistical analysis of 79 patients showed that the two patient subgroups also differed with regard to overall survival and a panel of known clinical prognostic factors including LDH, thymidine kinase serum levels and expression of the CD38 surface antigen by the leukemic cell clone. The level of ZAP-70 expression did not change over time in the majority of patients where sequential samples were available for analysis.
Dürig
J
J
Department of Hematology, University Hospital Essen, University of Duisburg-Essen, Germany.
Nückel
H
H
Cremer
M
M
Führer
A
A
Halfmeyer
K
K
Fandrey
J
J
Möröy
T
T
Klein-Hitpass
L
L
Dührsen
U
U
D036541:ADP-ribosyl Cyclase / Q000378:metabolism; D051997:ADP-ribosyl Cyclase 1; D015703:Antigens, CD / Q000378:metabolism; D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics*; D002999:Clone Cells; D005434:Flow Cytometry; D015971:Gene Expression Regulation, Enzymologic; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D008562:Membrane Glycoproteins; D011379:Prognosis; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D013937:Thymidine Kinase / Q000097:blood; D016896:Treatment Outcome; D051746:ZAP-70 Protein-Tyrosine Kinase; D001613:beta 2-Microglobulin / Q000097:blood
D015703:Antigens, CD; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D008562:Membrane Glycoproteins; D001613:beta 2-Microglobulin; D013937:Thymidine Kinase; D011505:Protein-Tyrosine Kinases; D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1