The role of apoptosis in the pathogenesis of the myelodysplastic syndromes.

The paradoxical occurrence of peripheral cytopenias despite a normo/hypercellular marrow in myelodysplastic syndromes (MDS) has been attributed to excessive intramedullary hematopoietic cell apoptosis. It has also been postulated that abrogation of programmed cell death (PCD) may underlie MDS transformation to acute myeloid leukemia (AML). Despite overwhelming evidence for a role of aberrant apoptosis in myelodysplasia, the molecular mechanisms responsible for such changes have not been elucidated. This paper summarizes current evidence implicating a role for altered PCD in MDS and outlines potential cellular mechanisms whereby hematopoietic progenitor cell apoptosis may be dysregulated.