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Abstract Numerous studies have indicated that the growth, differentiation, and survival of acute leukemia cells are regulated by intracellular and extracellular signals. Most signals that lead to apoptosis do so by activating intrleukin1 beta converting enzyme like proteases termed caspase. Caspase2 is an intracellular cysteine protease that exists as proenzyme (inactive), becoming activated during the cascade of events associated with apoptosis. Caspase2 mRNA can be spliced into two isoforms: the long form is proapoptotic while the short form is antiapoptotic This study aims: to determine the caspase2 activity in a number of patients with acute leukemia at diagnosis and correlate its proteolytic activity with clinical outcome and other laboratory variables. The present study comprised 36 leukemic patients besides 14 apparently healthy individuals as a control group. The patients were categorized as follows::group I: 13 patients with AML (7 males and 6 females, mean age: 42.2 (R+ (B18.6 years), group II: 15 patients with ALL (11 males and 4 females, mean age: 25.7 (R+ (B15.4 years) and group III: 8 patients with CML in blastic crisis (4 males and 4 females, mean age: 37.6 (R+ (B13.5 years). The results of this study could be summarized as follows: Caspase2 activity (before and after induction of apoptosis) was statistically and significantly lower in all patient groups when compared to controls. A significant difference in caspase2 activity was elicited among different FAB subtypes in both AML and ALL.. Patients with CML in blastic phase elicited a nonsignificant correlation between caspase2 activity in induced cells and all studied parameters. Conclusion: Caspase2 activity is low in patients with acute leukemia, suggesting that failure of apoptosis could be attributed to dysregulation of caspase activation pathways in leukemic patients. Caspase2 pathway dysregulation has a minor role in patients with CML in blastic crisis. Better outcome is associated with a higher activity of caspase2, suggesting that regardless of the upstream events that modulate the caspase pathways, caspase2 could be used as a predictor of achieving CR in acute leukemia. Fold increase of caspase2 activity above a critical threshold is strikingly related to the probability of achieving CR in patients with acute leukemia. |