Physiopathology of myelodysplastic syndromes

Myelodysplastic syndromes are clonal diseases of the hematopoietic stem cell with normal or increased bone marrow cellularity and peripheral cytopenias. Pathophysiology of these diseases is complex with frequent ras mutations, a growth defect of immature progenitors mainly erythroid progenitors, and increased apoptosis of differentiated cells. This growth defect could be linked to (1) a resistance to hematopoietic cytokine stimulation although, erythropoietin receptor expression and functionality are normal and/or (2) increased susceptibility to apoptosis due to overexpression of the death domain receptor Fas on CD34(+), CD33(+) and GPA(+) cells. Stromal cells are thought to produce increased quantities of inhibitory cytokines such as TNF-alpha, TGF-beta, IFNgamma et IL-1. Better understanding of MDS pathophysiology is required for applying adequate therapy either blocking apoptosis or stimulating hematopoiesis. (C) 2002 Editions scientifiques et medicales Elsevier SAS.