In b-cell chronic lymphocytic leukemia lymphocytes, in vitro effect of atorvastatin and rosiglitazon on cd38, zap 70, annexin v and bcl-2

OBJEKTIVE:CD38 and ZAP 70 expression have an important prognostic role in Chronic Lymphocytic Leukemia (CLL). Also the role of apopitozis is well known in the pathogenesis of CLL and it may direct the treatment. The studies on the effects of atorvastatin and rosiglitazon on lymphocytic apopitozis and immune system are increased. We aimed to determine the effects of these drugs on CD38, ZAP 70, annexin V, and Bcl-2 levels of CLL lymphocytes.MATERIALS AND METHODS: Seven (4 males) patients with CLL with average age 56±8 years were enrolled to the study. Of them 4 were in Binet A, 2 in Binet C, and 1 in Binet B. Hemoglobin levels of the patients were 12+-1.8 g/dL, hematocrit levels 35+-6%, platelet counts 156±68 x103/mm3, leukocyte counts 50.5±38.7 x103/mm3, and lymphocyte counts 45.7±38.1 x103/mm3. Patients with hypercholesterolemia, DM, and using drugs for these disorders were excluded. Mononuclear cells of blood samples from peripheral veins were separated by ficol method. On culture plate with 24 wells (1000000 cells/ml), it was suspended with 2 mlRPMI 1640. (20% human albumin, 2mM l-glutamin,100U/L penicillin, 100 ?g/ml streptomycin were added to RPMI). It was incubated for 24 hours in a 37 C and 5% CO2 'etüv. In these cells, the expressions of CD5, CD38,ZAP 70, and annexin V were evaluated with flow cytometry using EPICS XL-MCL instrument. These results were evaluated by two researcher as double-blind and means were calculated. Because CLL lymphocytes can die in vitro, 1 ng/ml IL-4 was added. 3 groups were formed. 5 micromolar atorvastatin suspension in first group and 2 micromolar rosiglitazon maleat in second group were added. The third group was used as control group. After 24 hours, the expressions of CD5, CD38, ZAP 70, and annexin V, the levels of Bcl-2 were reevaluated. Two-paired student t test was used for statistical analysis and p<0.05 was accepted as significance level. Adnan Menderes University ethic board approved the study.RESULTS: Atorvastatin and rosiglitazon did not affect CD38 expressions and Bcl-2 levels but Annexin V levels increase significantly when compared with control group (p<0.001). CD5 expression significantly decreases when compared with control group (p=0.03). ZAP 70 expression decreases with both drugs (p<0.05 for both).CONCLUSIONS: To determine the role of atorvastatin and rosiglitazon in CLL, extensive in vivo studies are needed.Key words: Chronic Lymphocytic Leukemia, apopitozis, atorvastatin, rosiglitazon