Physiopathologie des syndromes myélodysplasiques

Myelodysplastic syndromes are heterogeneous hematopoietic stem cell diseases characterized by myeloid dysplasia and increased apoptosis. Pathways to death targeting mitochondria are activated downstream the death receptor, Fas and the endoplasmic reticulum. Rare molecular events like overexpression of oncogenes, ectopic expression of non hematopoietic genes, gene expression in conditions of haploinsufficiency, identified in these diseases have been used to generate mouse models, which recapitulate the features of MDS or MDS/AML. These molecular defects may alter protein-RNA transport, ribosome biogenesis, transcription and signalling, leading to block of maturation, cellular stress and apoptosis. Clonal selection of hematopoietic stem cell requests a still unknown initiating event.