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Prognostic significance of new biological markers in chronic lymphocytic leukaemia

Leković Danijela, Mihaljević Biljana, Kraguljac-Kurtović Nada, Peruničić-Jovanović Maja, Bogdanović Andrija, Čolović Milica, Gotić Mirjana

Introduction. Chronic lymphocytic leukaemia is a disease with heterogeneous clinical course and outcome. Some patients have a progressive course of the disease and require therapy immediately after the diagnosis, while others have a stable form without the need for treatment. Recently, two new biological markers, the expression of CD38 antigen and ZAP-70 have shown independent significance in the prognosis in CLL patients. Objective. The aim of our study was to evaluate the clinical value of CD38 antigen and ZAP-70 expression as predictors of the disease progression and to analyze the correlation of these markers with other B-CLL prognostic markers. Methods. We assessed the expression of CD38 antigens by flow cytometry on peripheral blood samples and the expression of ZAP-70 by immunohistochemistry on formalin-fixed bone marrow (BM) biopsies in 40 newly diagnosed B-CLL patients. Disease progression was defined by the period elapsed from diagnosis to the time to first treatment (TFT). Results. Expression of CD38 antigen correlated positively with ZAP-70 expression (Pearson, r=0.476; p=0.002). Also, correlation analysis results showed that a positive expression of CD38 and ZAP-70 statistically significantly correlated with unfavourable classical prognostic parameters, such as advanced Binet stage C, diffuse BM infiltration, increased lactate-dehydrogenase and beta-2 microglobulin serum levels. Patients with positive expression of CD38 antigen and ZAP-70 had a shorter TFT (log rank, 0.003 vs. 0.049). Conclusion. Both new biological markers were shown to have an exceptional significance in the prediction of prognosis in CLL patients.

Keywords: chronic lymphocytic leukaemia, CD38 antigen, ZAP-70, prognosis