Spontaneous apoptosis in chronic lymphocytic leukemia and its relationship to clinical and cell kinetic parameters

Chronic lymphocytic leukemia (CLL) presents considerable variability in clinical presentation as well as in its evolution. In contrast to the inhibition of apoptosis in vivo, spontaneous apoptosis after short-term culture occurs. We studied the degree of this apoptosis in vitro, and its interactions with several clinical and laboratory parameters. Apoptosis was measured by the annexin V technique. Proliferation rate was evaluated by the AgNOR (nucleolar organizer regions) technique. There were inverse correlations between the percentage of annexin V-positive cells and peripheral lymphocyte count (r = - 0.49), Rai stage (r = - 0.40), Binet stage (r = - 0.50), TTM (total tumor mass score; r = - 0.51), and percentage of cells with one AgNOR cluster (r = - 0.45). Direct correlations were found with hemoglobin values ( r = 0.34) and platelet counts (r = 0.52). The number of CD8-positive cells showed a correlation with peripheral lymphocyte count (r = 0.49). When this variable was held constant, a correlation was detected between CD8-positive cells and staging (r = -0.47), TTM (r = - 0.42), and platelet count (r = 0.67). CD4-positive lymphocytes presented a correlation only with CD8-positive lymphocytes. In a cluster analysis, it was possible to create three groups of patients with different apoptosis rates using the TTM and AgNOR values. We conclude that, with the progression of the disease, together with the increase of tumor mass and proliferation rate, there is a decrease in the susceptibility to apoptosis.