Partitioning apoptosis: a novel form of the execution phase of apoptosis

Apoptosis is characterized by chromatin condensation, DNA cleavage, redistribution of phosphatidylserine, and apoptotic body formation via an actin-dependent process. We describe a novel form of the execution phase of apoptosis in human multiple myeloma cells that is morphologically and mechanistically distinct from classical apoptosis, but is caspase-dependent and inhibited by IL-6 and overexpression of Bcl-2. Electron microscopic analysis of these cells demonstrated chromatin condensation without nuclear fragmentation, and 'partitioning' of cell constituents into two components: a single, large bleb containing soluble protein and free ribosomes, and a region containing the nucleus, organelles, and RER. In some cases, the bleb separated, becoming a free vesicle exhibiting random kinetic motion. These morphologic features occurred despite inhibition of the actin and tubulin cytoskeletal systems. This novel form of apoptosis, called partitioning apoptosis, was observed in a variety of tumor cell types and in primary cells. The execution phase of apoptosis can occur in a manner that is morphologically and mechanistically distinct from classical apoptosis.