Biologic nature of the myelodysplastic syndromes

In the myelodysplastic syndromes (MDS) clonogenic marrow cell culture studies have demonstrated intrinsic hemopoietic stem cell and progenitor cell abnormalities consistent with these disorders representing clonal hemopathies. Abnormal responsiveness of these cells to stimulatory and inhibitory growth factors indicate the contribution of regulatory abnormalities in these patients. These in vitro growth abnormalities have prognostic import and the defects progress as subsets of these patients evolve into a blastic transformation stage. Maturation-inducing agents such as retinoic acid and vitamin D alter clonal growth patterns and enhance myeloid differentiation in the MDS, and correlations between in vitro and in vivo responsiveness of hemopoietic cells to retinoic acid have been demonstrated. Studies will be reviewed indicating the role of these biologic parameters for understanding pathogenetic mechanisms underlying the MDS.