The genetic basis of phenotypic heterogeneity in myelodysplastic syndromes

Myelodysplastic syndromes (MDS) are malignant clonal disorders of haematopoietic stem cells and their microenvironment, affecting older individuals (median age ∼70 years). Unique features that are associated with MDS - but which are not necessarily present in every patient with MDS - include excessive apoptosis in maturing clonal cells, a pro-inflammatory bone marrow microenvironment, specific chromosomal abnormalities, abnormal ribosomal protein biogenesis, the presence of uniparental disomy, and mutations affecting genes involved in proliferation, methylation and epigenetic modifications. Although emerging insights establish an association between molecular abnormalities and the phenotypic heterogeneity of MDS, their origin and progression remain enigmatic.