Apoptosis in chronic myelogenous leukemia: studies of stage-specific differences.
In this study we compared rates of apoptosis, survival and metabolic activity from CML peripheral blood neutrophils with peripheral blood and bone marrow neutrophils from healthy volunteer donors and studied the influence of the disease stage and of cytokines including G-CSF, GM-CSF and IL-1beta on these parameters. Quantification of apoptosis by morphology, diphenylamine DNA fragmentation assay and by gel electrophoresis showed similar rates of apoptosis in chronic phase CML and normal peripheral blood neutrophils when the cells were incubated in RPMI + FCS or in serum-free medium. However, there were lower rates of apoptosis in accelerated and blast phase CML neutrophils (p < .001) and in normal bone marrow neutrophils (p < .001) compared to normal peripheral blood neutrophils (incubated in RPMI + FCS). Survival among neutrophils from chronic phase or accelerated/blast phase CML patients was significantly longer (p < 0.002 and p < 0.001, respectively) than among normal peripheral blood neutrophils but neutrophils purified from normal bone marrow had a survival rate which fell between that of normal peripheral blood and chronic phase CML patients. When the cells were incubated in RPMI + autologous sera, neutrophils from chronic phase CML patients showed markedly lower rates of apoptosis (p < 0.001) and maintained higher metabolic activities (p < 0.002) compared to normal neutrophils. G-CSF and GM-CSF were found to considerably decrease the rate of apoptosis in chronic phase CML neutrophils (p < 0.001 and p = 0.008 respectively) while IL-1beta 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 progression of CML.
Gisslinger
H
H
Department of Clinical Investigation, University of Texas, M.D. Anderson Cancer Center, Houston 77030, USA.
Kurzrock
R
R
Wetzler
M
M
Tucker
S
S
Kantarjian
H
H
Robertson
B
B
Talpaz
M
M
D000328:Adult; D000368:Aged; D017209:Apoptosis; D001752:Blast Crisis; D002470:Cell Survival; D053938:DNA Fragmentation; D004273:DNA, Neoplasm / Q000737:chemistry; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000166:cytology* / Q000378:metabolism / Q000473:pathology; D014407:Tumor Cells, Cultured / Q000648:ultrastructure
D004273:DNA, Neoplasm; D007375:Interleukin-1; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor