Analysis of TRAIL-induced apoptosis in acute myeloid leukemia cells

Abstract

Advanced tumors, including leukemia, represent heterogeneous cell populations evolved from original malignant clones. Chemotherapy of leukemia is often associated with selection of drug-resistant cells followed by progression/relapse of the disease. Implementation of molecules that specifically target leukemia cells with minimal toxicity to normal tissues might significantly improve outcome of leukemia treatment. TRAIL belongs to the tumor necrosis factor (TNF) ligand family of cytokines. TRAIL triggers apoptosis in target cells via the receptor-mediated apoptotic pathway. Receptors for TRAIL can be divided into death receptors, TRAILR1/ DR4 , TRAIL-R2/DR5, and decoy receptors, TRAIL-R3/DcR1, TRAIL-R4/DcR2, osteoprotegerin/OPG/TRAIL-R5, based on their ability to transduce apoptotic signal. While normal tissues, including hematopoietic progenitor cells, are resistant to TRAIL-induced apoptosis, TRAIL induces programmed death in many tumor cell lines and primary cells. Various malignant cell lines and primary tumor cells, however, show resistance to TRAIL-induced apoptosis. TRAIL-resistance could represent important limitation for the potential TRAIL anti-tumor therapy. Combined in vitro application of TRAIL with other anti-cancer agents often increased sensitivity or overcame resistance of the tumor cells to...