Mechanisms of Action of Hypomethylating Agents: Endogenous Retroelements at the Epicenter.

ABSTRACT: Abnormal DNA methylation patterns are thought to drive the pathobiology of high-risk myelodysplastic syndromes (HR-MDS) and acute myeloid leukemia (AML). Sixteen years after their initial approval, the hypomethylating agents (HMAs), 5-azacytidine (AZA) and 5-aza-2'-deoxycytidine, remain the mainstay of treatment for HR-MDS and AML. However, a connection of the hypomethylating or additional effects of HMAs with clinical responses remains yet to be shown, and the mode of action of HMAs remains obscure. Given the relatively short-lived responses and the inevitable development of resistance in HMAs, a thorough understanding of the antineoplastic mechanisms employed by HMAs holds critical importance. Recent data in cancer cell lines demonstrate that reactivation of endogenous retroelements (ERE

SUBMITTER: Kordella C 

PROVIDER: S-EPMC7985079 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature