Granulocyte apoptosis in patients with thalassemia

9. SUMMARY GRANULOCYTE APOPTOSJS IN PATIENTS WITH THALASSEMIA Ineffective erythropoesis is the major defect that leads to anemia in beta- thalassemia patients. The enhanced apoptosis secondary to increased a-globin accumulation in erythroid progenitors is the main cause of ineffective erythropoesis in beta-thalassemia. In a recent study, enhanced apoptosis was clearly demonstrated in erythroid progenitors in patients with beta-thalassemia, but in lymphoid and granulocyte precursors, enhanced apoptosis could not be found. Oxidative stress causes apoptosis in cells. Oxidative stress exists in thalassemic serum as evidenced by the presence of high level of lipid peroxides, low level of vitamin E and low level of antioxidant enzymes. Morphological signs of apoptosis are demonstrated on endothelial cells incubated with thalassemic serum. Also defective migration and chemotaxis functions of neutrophils of thalassemia patients were reported in the literature. Iron overload is one of the factors that causes defective granulocyte functions and susceptibility to infections. Serum ferritin, not the other iron carrying compounds exerts toxic effect on granulocyte membrane function. Desferrioxamine (DFO) is widely used in the treatment of transfusion related iron overload. It's well known that DFO is a cytotoxic agent which inhibits S-phase of cell proliferation, prevents DNA synthesis and leads apoptosis of cells in culture.The aim of this study was to investigate apoptosis rate of peripheral granulocytes with Annexin-V method and to examine the association between the granulocyte apoptosis and frequency of infections, the role of DFO treatment, and serum ferritine levels. This study was performed between June 2001 and August 2001. Twenty two thalassemic children receiving DFO treatment, thirteen thalassemic children not receiving DFO treatment, and fifteen healthy children as the control group were included in this study. In all children, granulocytes were isolated by using Histopaque-1119 and Histopaque-1077 from peripheral blood samples. Granulocyte apoptosis was studied with Annexin V-FITC apoptosis detection method. As a result of our study, we concluded that apoptosis of peripheral granulocytes is not increased in beta-thalassemia patients and there is no association between the granulocyte apoptosis and frequency of infections, role of DFO chelation therapy and high serum ferritine levels. 34