TRAIL-induced apoptosis of HL60 leukemia cells: Two distinct phenotypes of acquired TRAIL resistance that are accompanied with resistance to TNFa but not to idarubicin and cytarabine

0334040 - ÚMG 2010 RIV US eng J - Journal Article
Klener, P.Jr. - Leahomschi, S. - Molinsky, J. - Simonova, T. - Nečas, E. - Gašová, Z. - Čermák, J. - Doležalová, L. - Anděra, Ladislav - Živný, J.
TRAIL-induced apoptosis of HL60 leukemia cells: Two distinct phenotypes of acquired TRAIL resistance that are accompanied with resistance to TNFa but not to idarubicin and cytarabine.
Blood Cells Molecules and Diseases. Roč. 42, č. 1 (2009), s. 77-84. ISSN 1079-9796. E-ISSN 1096-0961
R&D Projects: GA MŠMT 1M0506
Grant - others:GA MŠk(CZ) LC06044; GA MZd(CZ) NR8317
Program: NR
Institutional research plan: CEZ:AV0Z50520514
Keywords : TRAIL resistance * leukemia * therapy
Subject RIV: EB - Genetics ; Molecular Biology
Impact factor: 2.901, year: 2009

TNF-related apoptosis-inducing ligand (TRAIL) is a proapoptotic cytokine implicated in cancer cell surveillance. Prolonged exposure of TRAIL-sensitive leukemia cell line HL60 cells to recombinant TRAIL or to cytostatic agents, cytarabine and idarubicin, resulted in the establishment of resistant subclones with distinct phenotypes. The TRAIL resistant subclones had decreased expression of TRAIL and TNFa death receptors, impaired activation of caspases 8 and 10 in response to TRAIL and TNFa and dysregulated expression of several apoptosis regulators. TRAIL resistant HL60 showed two phenotypes with different expression of CD14, osteoprotegerin, and several apoptosis regulators and were resistant to TNFa, suggesting disruption of the extrinsic apoptotic pathway. The concurrently derived cytarabine and idarubicin-resistant HL60 subclones remained sensitive to TRAIL-induced apoptosis. We identified distinct pathways for the development of HL60 leukemia cell resistance to apoptosis induction.
Permanent Link: http://hdl.handle.net/11104/0178875