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Chronic lymphocytic leukemia is disease with very heterogeneous clinical course, some patients have long survival without treatment, while others have short survival in spite of intensive treatment. Therefore is important to predict clinical outcome at the time of diagnosis and to plan adequate therapy. Classic prognostic parameters is based on tumor size and are not valid for prognosis in the early clinical stages. CD38, ZAP-70, CD49d and CXCR4 are involved in cell signalization and interactions with microenvironment. This molecules conduct proliferative and anti-apoptotic signals and contribute to the development of the disease and resistance to treatment. Expression of CD38, ZAP-70, CD49d and CXCR4 correlates with active subpopulation of  leukemic clone and can predict course of the chronic lymphocytic leukemia at the time of diagnosis.

Aim of the study was to determine if there is a correlation of CD38, ZAP-70, CD49d and CXCR4 expression in chronic lymphocytic leukemia and if there is a correlation between expression of these antigens with clinical and laboratory parameters.

40 patients with chronic lymphocytic leukemia was analysed before treatment. Expression of CD38, ZAP-70, CD49d and CXCR4 was detected by immunocytochemical staining. Correlation of expression of the CD38, ZAP-70, CD49d, CXCR4, and correlation between expression of these antigens and clinical and laboratory parameters were tested with standard statistical methods.

Median age of patients was 61,8 years; 14 patients were in Binet stage A, 14 in Binet stage B and 12 in Binet stage C. Median total lymphocyte count was 38,8x10.9/l. Among all patients, CD38 positive were 45%, ZAP-70 positive 55%, CD49d positive 52,5% and mean percent of CXCR4 positive cells was 57,2% cells. There were statistically significant correlations between CD38 and ZAP-70 positivity, CD38 and CD49d positivity, and ZAP-70 and CD49d positivity. There were also correlation between percentage of cells which express CD38, ZAP-70 and CD49d, and correlation between percentage of cells which express CD49d and CXCR4. Expression of ZAP-70 correlate with advanced clinical stage and hepatomegaly, expression of CD49d with hepatomegaly, and expression of CD38 with number of lymph nodes and splenomegaly.

In our study, expression of CD49d in chronic lymphocytic leukemia cells strongly correlates with expression of CD38 and ZAP-70, and CD49d expression correlates with CXCR4 expression, suggesting cooperation of these molecules in leukemic cell functions.