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B-CLL

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

Abstract

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.

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Acknowledgements

We thank Ute Schmücker for expert technical assistence with flow cytometry and Brigitte Fischer for her help with compiling patient data.

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Dürig, J., Nückel, H., Cremer, M. et al. ZAP-70 expression is a prognostic factor in chronic lymphocytic leukemia. Leukemia 17, 2426–2434 (2003). https://doi.org/10.1038/sj.leu.2403147

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