Targeting IAP Proteins to Sensitize Childhood Acute Leukemia Cells for Apoptosis

XIAP, a member of „Inhibitor of Apoptosis“ (IAP) proteins, may present a suitable molecular target for therapeutic intervention, since it is expressed at high levels in acute leukemia and blocks apoptosis at a central point of the apoptotic machinery. Here, we report that neutralizing XIAP by small molecule inhibitors is a novel and effective approach to sensitize childhood acute leukemia cells for TRAIL-induced apoptosis. XIAP inhibitors at subtoxic concentrations synergize with TRAIL to induce apoptosis in acute lymphoblastic leukemia cells and to reduce clonogenic growth. Analysis of signaling pathways reveal…