Decitabine in Myelodysplastic Syndromes

Excerpt

5-aza-2′-deoxycytidine (decitabine) is a nucleoside analogue with the capacity to induce global and gene-specific DNA hypomethylation. It exerts this effect by trapping DNA methyltransferase to DNA. This hypomethylating effect is DNA replication dependent. DNA methylation is an epigenetic modification of DNA that has a role in the control of gene expression regulation. Aberrant DNA methylation of multiple promoter cytosone phosphoguanine (CpG) islands is a common characteristic of cancer and leukemia, and in particular of myelodysplastic syndrome (MDS). Interest in the use of hypomethylating in MDS is derived from the realisation that aberrant DNA methylation is reversible, and that this process is associated with gene reactivation. Based on this concept, a significant effort is underway to develop drugs with hypomethylating activity as antineoplastic agents. Indeed, the first drug approved for MDS was 5-azacitidine, another hypomethylating nucleoside analogue.[1] …