ZAP-70 expression is a prognostic factor in chronic lymphocytic leukemia

• DOI: 10.1038/sj.leu.2403147
• Publication Date: 2003-10-02T13:18:13Z
• Authors: J Dürig; H Nückel; M Cremer; A Führer; K Halfmeyer; J Fandrey; T Möröy; L Klein-Hitpass; U Dührsen
• Keywords: Membrane Glycoproteins; ZAP-70 Protein-Tyrosine Kinase; Gene Expression Regulation, Leukemic; Reverse Transcriptase Polymerase Chain Reaction; Medizin; Antineoplastic Agents; Protein-Tyrosine Kinases; Flow Cytometry; Prognosis; ADP-ribosyl Cyclase 1; Leukemia, Lymphocytic, Chronic, B-Cell; Thymidine Kinase; Gene Expression Regulation, Enzymologic; Clone Cells; 03 medical and health sciences; Treatment Outcome; 0302 clinical medicine; Antigens, CD; Risk Factors; Biomarkers, Tumor; Humans; ADP-ribosyl Cyclase; Retrospective Studies

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.