Epigenetic dysregulation in myelodysplastic syndromes

Myelodysplastic syndrome (MDS) is a clonal hematopoietic stem cell disease characterized by impaired hematopoiesis and an increased risk of transformation to acute myeloid leukemia (AML). Epigenetic regulators, including TET2, DNMT3A and EZH2, are often mutated in patients with MDS. Recently, exome sequencing of blood cells from aged people without hematological malignancies have demonstrated the presence of clonal hematopoiesis with myeloid malignancies-associated mutations, such as TET2 and DNMT3A. Here, I will discuss the molecular mechanisms underlying the accumulation of epigenetic alterations and genetic mutations, including TET2, DNMT3A and EZH2, and how these promote the development of MDS and hematological malignancies in aged people with clonal hematopoiesis.