Abstract
Reactive oxygen species (ROS) including hydrogen peroxide (H&sub2;O&sub2;) exhibit both pro-survival and pro-death signaling in leukemic cells. We examined the effect of exogenous H&sub2;O&sub2; on Fas ligand (FasL) -induced apoptosis in Jurkat cells. H&sub2;O&sub2; applied prior to (pre-conditioning) and during (post-conditioning) FasL stimulation attenuated early apoptosis through activation of EKR5. H&sub2;O&sub2; increased the activated caspase-8 sequestered in the mitochondria thereby decreasing cell death through the extrinsic apoptotic pathway. In addition, inhibition of a protein tyrosine phosphatase likely explains the post-conditioning requirement for H&sub2;O&sub2;. Given that chemotherapeutic agents used for the treatment of acute lymphoblastic leukemia are thought to work partly through production of ROS, a simultaneous inhibition of the ERK5 pathway may abrogate the ROS-initiated pro-survival signaling for an enhanced cell kill.