The non-apoptotic role of caspase-9 promotes differentiation in leukemic cells.

Caspase family contains cysteine proteases involving in the key cellular processes, such as apoptosis, inflammation, and autophagy. There is a growing body of evidence that caspase family also plays a role in cellular differentiation. Evidence suggests that caspase-9 is among the most important members with non-apoptotic roles in the execution of differentiation. Since drug-induced differentiation in some types of cancer cells is a promising treatment, we have investigated caspase-9 activity during differentiation of a cancer cell; leukemia. We demonstrate that caspase-9 has increased activity during differentiation and also the inhibition of caspase-9 will prevent the granulocytic differentiation of leukemic cells. In addition, we studied the differentiation induction mediated by caspase-9 using an inducible variant of caspase-9. Results indicate the caspase-9 mediated differentiation accompanied by a reduction in the expression of CD33 and an increase in CD15. Notably, all of the events occur when cell viability remains constant. Owing to the evidence, caspase-9 activity is considered as a central factor in the execution of differentiation in leukemic cells.