Lingering biologic dilemmas about the status of the progenitor cells in myelodysplasia

Myelodysplastic syndromes (MDS) are considered to be stem cell disorders. High incidence of intramedullary apoptosis has been associated with the peripheral cytopenia and refractory anemia in these disorders. The investigations on the cell of origin in the bone marrow have invariably been hampered by a poor yield of CD34+ cells from these marrows. Interestingly, even though limited in number, these studies raised more questions and dilemmas than providing answers. While the enigma surrounding the clonality of these marrows continues, the controversies regarding incidence of apoptosis, proliferation, and potential of clonogenic expansion may be closer to a settlement. The present review proposes a model depicting interplay between extraneous apoptogenic factors and intracellular apoptosis-susceptibility determinants that contributes significantly toward the progression of MDS and how a shift in dynamics of this interplay may provide grounds to accumulate additional mutations with a probable block in differentiation eventually leading to a leukemic transformation.