[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, IFN gamma et IL-1. Better understanding of MDS pathophysiology is required for applying adequate therapy either blocking apoptosis or stimulating hematopoiesis.
Claessens
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YE
Laboratoire d'Hématologie AP-HP et Département d'Hématologie, Institut Cochin, INSERM CNRS, Université René Descartes, Hôpital Cochin, 27, rue du Faubourg Saint-Jacques, 75679 Paris, France.
Fontenay-Roupie
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M
D017209:Apoptosis; D001854:Bone Marrow Cells / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D009190:Myelodysplastic Syndromes / Q000503:physiopathology*; D017467:Receptors, Erythropoietin / Q000096:biosynthesis
D016207:Cytokines; D017467:Receptors, Erythropoietin