KRN5500 exposure to CLL cells in vitro causes caspase-dependent apoptosis via the intrinsic but not the extrinsic pathway of apoptosis and no change in Bcl-2 expression. (A) Expression of caspase-9 zymogen protein (48 kDa) in human CLL cells at 24 hours following incubation with medium or KRN5500 (0.134 or 1.34 μM) demonstrating processing of caspase-9 (and, thus, decrease in 45 kDa band), a finding supportive of activation of the intrinsic pathway of apoptosis. (B) Expression of caspase-8 zymogen protein (55 kDa) in human CLL cells at 24 hours following incubation with medium or KRN5500 (0.134 or 1.34 μM) demonstrating no processing of procaspase-8 (and, thus, no decrease in 55 kDa band), a finding supportive of KRN5500 apoptosis occurring independent of the extrinsic pathway of apoptosis. (C) Expression of the Bcl-2 protein in human CLL cells at 24 hours following incubation with KRN5500 (0.134 or 1.34 μM) demonstrating no change in Bcl-2 expression following treatment with this agent.