earticle

영어

Tumor necrosis factor (TNF)-related apoptosis inducing ligand (TRAIL) has received great attention in recent years as a potential treatment. Previous studies have shown that primary acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) blasts show a variable but overall poor response to TRAIL mediated cytotoxicity. Here we reported that KD548-Fc,
a novel agonistic Kringle domain against DR4/5, possessed a strong cytotoxic activity in AML and ALL cell lines. KD548-Fc induces caspase-independent cell death in TRAIL-sensitive and –resistant cell lines, whereas TRAIL induces caspase-dependent cell death in only TRAIL – sensitive cell lines. The present study demonstrates that reactive oxygen species (ROS) were
generated in Molt-4 and KG-1 cells upon KD548-Fc stimulation and that ROS accumulation subsequently evoked sustained activation of c-Jun Nterminal kinase (JNK). The reducing agent, N-acetylcysteine (NAC), effectively inhibited the sustained activation of JNK. These data provide
novel information of the DR4/5 –mediated cell death-signaling pathway and may shed new light on effective strategies for AML and ALL tumor therapies.