Myelodysplastic syndromes: the complexity of stem-cell diseases

Myelodysplastic syndromes (MDS) comprise the most common malignant blood disorder. MDS are increasing in frequency owing to an ageing population and increased awareness of these diseases.MDS are characterized by ineffective haematopoiesis. The bone marrow cells seem to be abnormal, with dysplastic changes in the nucleus or cytoplasmic granules.MDS can evolve from a refractory anaemia to acute myeloid leukaemia (AML), which is associated with a decrease in intramedullary apoptosis and a block in myeloid differentiation.Previously known as 'preleukaemia' or 'smouldering leukaemia,' MDS can be distinguished from de novo AML through its suppression of normal haematopoiesis, the presence of apoptosis in the early stages of the disease, the presence of chromosome 5 or 7 abnormalities, the incidence of blast cells being less than 20%, normal cellular differentiation at onset, a poorer response to treatment with cytosine arabinoside and an older age at presentation.One of the mysteries of MDS is how the stem cells that give rise to these syndromes differ from that of the AML stem cell. Although there are several genetically-defined mouse models of MDS, MDS stem cells are difficult to engraft in a xenotransplantation model.MDS that arises in paediatric patients might be secondary to inherited bone marrow-failure syndromes (for example, Fanconi anaemia, severe congenital neutropaenia, Shwachman–Diamond syndrome or Diamond–Blackfan anaemia).Most cases of adult MDS are sporadic, but some are due to exposure to genotoxic damage incurred during treatment with chemotherapy or ionizing radiation (therapy-related MDS; tMDS).Allogeneic stem-cell transplant is the only known cure. Newer drug therapies have been directed toward reversing gene silencing by hypomethylating agents (5′-azacitidine or decitabine) or through alteration of the cytokine environment by lenalidomide.