Apoptosis in the myelodysplastic syndromes

Myelodysplastic syndromes (MDS) are neoplastic dyscrasias characterized by peripheral cytopenia, despite a normocellular or hypercellular bone marrow. In the past decade, it has become apparent that this ineffective hemopoiesis is largely caused by excessive apoptosis of myeloid precursors. There is no evidence for gain-of-function mutations within the apoptotic machinery in MDS. It appears that the apoptosis is a reactive phenomenon fueled by cytokines. The provoking stimulus for the proapoptotic intramedullary milieu in MDS is unknown. The evolution of MDS from early relatively chronic to aggressive and frankly leukemic phenotype is accompanied by a suppression of apoptosis. This metamorphosis correlates with changes in intracellular levels of Bcl-2-family proteins, but the genetic basis for this shift has not been elucidated clearly. Expression profiling and proteomic technologies may offer the best means to unravel this process.