For epistasis analysis and to position caspase-2 in the chain of events, we exploited a set of human Nalm6 pre-B ALL cells lacking initiator caspase-8 or caspase-9, as well as cells lacking both effector caspases, caspase-3 and caspase-7, and compared their response to Nalm6 cells lacking caspase-2. Here, CASP2 is linked to acute lymphoblastic leukemia.