Apaf-1 protein deficiency confers resistance to cytochrome c-dependent apoptosis in human leukemic cells

The human leukemia cell lines K562, GEM, CEM/VB100, human leukemic blasts, and the bladder cancer J82 cell line have different sensitivities to UV lig ht-induced apoptosis. It is reported that resistance to UV light-induced ap optosis occurs at a point in the apoptotic pathway upstream of caspase-3 bu t downstream of mitochondrial cytochrome c release. It is demonstrated that the block is due to deficiency of Apaf-1, a critical member of the apoptos ome. Sensitivity to apoptosis was independent of caspase-9b or XIAP (inhibi tors of apoptosis proteins) expression or levels of procaspase-9. Transfect ion of Apaf-1 conferred sensitivity to apoptosis in resistant cells. Apaf-1 deficiency may constitute a significant mode of resistance to apoptosis in human leukemia (C) 2001 by The American Society of Hematology.