Evaluation of Apaf-1 and procaspases-2,-3,-7,-8, and-9 as potential prognostic markers in acute leukemia

Recent studies have suggested that variations in levels of caspases, a fami ly of intracellular cysteine proteases, can profoundly affect the ability o f cells to undergo apoptosis, In this study, immunoblotting was used to exa mine levels of apoptotic protease activating factor-1 (Apaf-1) and procaspa ses-2, -3, -7, -8, and -9 in bone marrow samples (at least 80% leukemia) ha rvested before chemotherapy from adults with newly diagnosed acute myelogen ous leukemia (AML, 42 patients) and acute lymphocytic leukemia (ALL, 18 pat ients). Levels of each of these polypeptides varied over a more than in-fol d range between specimens. In AML samples, expression of procaspase-2 corre lated with levels of Apaf-1 (R-s = 0.52, P < .02), procaspase-3 (R-s = 0.56 , P < .006) and procaspase-8 (R-s = 0.64, P < .002). In ALL samples, expres sion of procaspases-7 and -9 was highly correlated (R-s = 0.90, P < .003). Levels of these polypeptides did not correlate with prognostic factors or r esponse to induction chemotherapy, In further studies, 16 paired samples (1 3 AML, 3 ALL), the first harvested before induction therapy and the second harvested at the time of leukemia regrowth, were also examined. There were no systematic alterations in levels of Apaf-1 or procaspases at relapse com pared with diagnosis. These results indicate that levels of initiator caspa ses vary widely among different leukemia specimens but cast doubt on the hy pothesis that this variation is a major determinant of drug sensitivity for acute leukemia in the clinical setting. (C) 2000 by The American Society o f Hematology.