APOPTOSIS IN CHRONIC MYELOGENOUS LEUKEMIA - STUDIES OF STAGE-SPECIFICDIFFERENCES

In this study we compared rates of apoptosis, survival and metabolic a ctivity from CML peripheral blood neutrophils with peripheral blood an d bone marrow neutrophils from healthy volunteer donors and studied th e influence of the disease stage and of cytokines including G-CSF, GM- CSF and IL-1 beta on these parameters. Quantification of apoptosis by morphology, diphenylamine DNA fragmentation assay and by gel electroph oresis showed similar rates of apoptosis in chronic phase CML and norm al peripheral blood neutrophils when the cells were incubated in RPMI + FCS or in serum-free medium. However, there were lower rates of apop tosis in accelerated and blast phase CML neutrophils (p < .001) and in normal bone marrow neutrophils (p < .001) compared to normal peripher al blood neutrophils (incubated in RPMI + FCS), Survival among neutrop hils from chronic phase or accelerated/blast phase CML patients was si gnificantly longer (p < 0.002 acid p < 0.001, respectively) than among normal peripheral blood neutrophils but neutrophils purified from nor mal bone marrow had a survival rate which fell between that of normal peripheral blood and chronic phase CML patients. When the cells were i ncubated in RPMI + autologous sera, neutrophils from chronic phase CML patients showed markedly lower rates of apoptosis (p < 0.001) and mai ntained higher metabolic activities (p < 0.002) compared to normal neu trophils. G-CSF and GM-CSF were found to considerably decrease the rat e of apoptosis in chronic phase CML neutrophils (p < 0.001 and p = 0.0 08 respectively) while IL-1 beta did not show any antiapoptotic effect . It is suggested that the endogenous production of growth factors may therefore participate in delaying apoptotic cell death, during the pr ogression of CML.