Myelodysplastic Syndromes (MDS) are the topic of this ‘mechanisms of disease’ review in the New England Journal of Medicine. The primary MDS are one of five major categories of myeloid neoplasms; the main feature of which is stem-cell–derived clonal myelopoiesis with altered proliferation and differentiation. In this review, the authors discuss the following topics:

• Population at risk

• Pathological features

• Classification

• Diagnosis

• Karyotypic abnormalities

• Pathogenesis

• Clonality and the stem cell

• Mutations

• Mouse models

• The 5q minus syndrome, del(5q), and haploinsufficiency

• Global gene-expression studies

• Single-nucleotide polymorphisms

• Ineffective haematopoiesis, accelerated apoptosis, and bone marrow stroma

• Epigenetic changes

• Altered immune responses

• Leukemic transformation

• Prognostic scoring

• Treatment