A schematic model of apoptosis signaling in low-risk MDS progenitor cells.

The model proposes that the increased sensitivity to ligation of death receptors evidenced in MDS progenitor cells is due to the sensitization of these cells by constitutive activation of the mitochondrial axis. Triggering of death receptors, such as Fas, or direct targeting of mitochondria, results in the release of cytochrome c and downstream activation of caspase-9 via apoptotic protease-activating factor 1 (Apaf-1)–mediated apoptosome formation. G-CSF exerts its antiapoptotic—and hence its erythrogenic—effect by interfering with this mitochondria-dependent pathway.