Pathogenetic mechanism

The clonal myeloid haemopathies, including myelodysplastic syndromes (MDS), comprise a group of disorders whose phenotypic expression relates to abnormal haemopoietic regulation. Targets of this dysregulation include cellular programmes for stem cell survival, proliferation, differentiation, and inhibition. The dysregulation occurring in MDS is related to both abnormalities within the patients' haemopoietic stem cells and in their marrow stromal support mechanisms.1 ,2

The stem cell abnormalities in MDS include altered levels of apoptosis (programmed cell death), immune dysregulation, telomere shortening, and enhanced oxidative stress susceptibility. The marrow stromal derangements in this disorder, which enhance apoptosis, include increased paracrine production of inhibitory cytokines (for example, tumour necrosis factor α (TNFα), transforming growth factor β, Fas ligand) and suboptimal production of stimulatory cytokines (G-CSF, GM-CSF, interleukin 3, erythropoietin), which together diminish the survival and …