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

摘要: Recent studies have suggested that variations in levels of caspases, a family intracellular cysteine proteases, can profoundly affect the ability cells to undergo apoptosis. In this study, immunoblotting was used examine apoptotic protease activating factor-1 (Apaf-1) and procaspases-2, -3, -7, -8, -9 bone marrow samples (at least 80% leukemia) harvested before chemotherapy from adults with newly diagnosed acute myelogenous leukemia (AML, 42 patients) lymphocytic (ALL, 18 patients). Levels each these polypeptides varied over more than 10-fold range between specimens. AML samples, expression procaspase-2 correlated Apaf-1 (R(s) = 0.52, P <.02), procaspase-3 0.56, <.006) procaspase-8 0.64, <.002). ALL procaspases-7 highly 0.90, <.003). did not correlate prognostic factors or response induction chemotherapy. further studies, 16 paired (13 AML, 3 ALL), first therapy second at time regrowth, were also examined. There no systematic alterations procaspases relapse compared diagnosis. These results indicate initiator caspases vary widely among different specimens but cast doubt on hypothesis variation is major determinant drug sensitivity for clinical setting. (Blood. 2000;96:3922-3931)