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CLL

Combined analysis of ZAP-70 and CD38 expression as a predictor of disease progression in B-cell chronic lymphocytic leukemia

Leukemia volume 19, pages 750–758 (2005)Cite this article

Abstract

Prognostic predictions in B-cell chronic lymphocytic leukemia (B-CLL) at early clinical stage are based on biological disease parameters, such as ZAP-70 and CD38 protein levels, genomic aberrations as well as immunoglobulin variable heavy chain gene (IgVH) mutation status. In the current study, ZAP-70 and CD38 expressions were examined by flow cytometry in 252 patients with B-CLL. Cytoplasmic ZAP-70 expression in more than 20% (ZAP-70+) and surface CD38 expression on more than 30% (CD38+) of B-CLL cells were associated with an unfavorable clinical course. The levels of ZAP-70 and CD38 did not change over time in the majority of patients where sequential samples were available for analysis. Combined analysis of ZAP-70 and CD38 yielded discordant results in 73 patients (29.0%), whereas 120 patients (47.6%) were concordantly negative and 59 patients (23.4%) were concordantly positive for ZAP-70 and CD38 expression. Median treatment-free survival times in patients whose leukemic cells were ZAP-70+CD38+ was 30 months as compared to 130 months in patients with a ZAP-70−CD38− status. In patients with discordant ZAP-70/CD38 results, the median treatment-free survival time was 43 months. Thus, ZAP-70 and CD38 expression analyses provided complementary prognostic information identifying three patient subgroups with good, intermediate and poor prognosis. Over-representation of high-risk genomic aberrations such as 17p deletion or 11q deletion and distribution of the IgVH mutation status in B-CLL discordant for ZAP-70/CD38 pointed toward a distinct biologic background of the observed disease subgroups. This finding was also supported by microarray-based gene expression profiling in a subset of 35 patients. The expression of 37 genes differed significantly between the three groups defined by their expression of ZAP-70 and CD38, including genes that are involved in regulation of cell survival and chemotherapy resistance.

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Acknowledgements

We thank Anja Führer, Ute Schmücker, Barbara Friedmann, Sabrina Becker, Frederike von Bonin and Rainer Steffens for excellent technical assistance and Brigitte Fischer for help with compiling patient data. We thank Dres Söling, Siehl, Burghardt, Nusch, Kalhori, Rudolph, Meyer, Detken and Seraphin for referring patients. This study was in part supported by the ‘Ministerium für Schule, Wissenschaft und Erziehung des Landes Nordrhein-Westfalen’. RS is supported by a grant from the Deutsche Krebshilfe (70-3138-Schr 1, Max-Eder-Programm).

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Authors and Affiliations

  1. Department of Hematology and Oncology, Georg-August-University, Goettingen, Germany

    R Schroers, F Griesinger, L Trümper & D Haase

  2. Department of Genetic Epidemiology, Georg-August-University, Goettingen, Germany

    B Kulle

  3. Institute of Cell Biology, University Hospital Essen, Germany

    L Klein-Hitpass

  4. Department of Hematology, University Hospital Essen, University of Duisburg-Essen, Germany

    L Sellmann, U Dührsen & J Dürig

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  1. R Schroers
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Correspondence to R Schroers or J Dürig.

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Schroers, R., Griesinger, F., Trümper, L. et al. Combined analysis of ZAP-70 and CD38 expression as a predictor of disease progression in B-cell chronic lymphocytic leukemia. Leukemia 19, 750–758 (2005). https://doi.org/10.1038/sj.leu.2403707

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