Laboratoire d'hématologie et service d'hématologie, AP-HP, université René-Descartes, Paris V, et département d'hématologie, institut Cochin, Inserm U. 567, hôpital Cochin, 27, rue du Faubourg-Saint-Jacques, 75679 Paris cedex 14.
Myelodysplatic syndromes are clonal acquired diseases of the haematopoietic stem cell with normal or increased bone marrow cellularity and peripheral cytopenias. A major characteristic is a growth defect of immature progenitors mainly erythroid progenitors. This growth defect has been linked to a partial resistance to haematopoietic cytokine stimulation although, for instance, erythropoietin receptor expression and functionality are normal. More recently, an increased susceptibility to apoptosis has been documented. Increased apoptosis is observed in low risk myelodysplasia and decrease with blastic evolution. All three haematopoietic lineages are implicated in the process. Caspase activation has been documented. The real implication of the haematopoietic stem cell is still unresolved. An important role of a deregulated Fas/Fas ligand system is suggested in the mechanism of apoptosis. Stromal cells that produce increased quantities of inhibitory cytokines such as TNF-alpha and IFN-gamma may also have a role in apoptosis. Treatment with anti-apoptotic drugs (hematopoietic growth factors, Thalidomide, anti-TNF-alpha antibodies) can improve cytopenias in selected patients, suggesting that a better understanding of apoptosis in MDS is required for applying adequate therapy.