[Biomarkers predicting the efficacy of DNA hypomethylating agents in the treatment of myelodysplastic syndromes and acute myeloid leukemia: TET enzymes].

Azacitidine (AZA), a hypomethylating agent, is widely used in patients with high-risk (HR) myelodysplastic syndromes (MDS). AZA is also believed to aid in the treatment of acute myeloid leukemia (AML). In randomized clinical trials for MDS, major and overall response rates for AZA alone were 16-33% and 38-60%, respectively. In the AZA-001 trial, the median overall survival (OS) for the AZA group was >24 months compared to 15 months for the control. However, other clinical trials have reported OS periods of 15-21 months, while population-based studies have reported OS rates much shorter than 20 months. Only a fraction of HR-MDS patients appears to benefit from AZA treatment. Furthermore, despite its low-intensity nature, the risk may outweigh the benefit in a significant proportion of patients; therefore, the indication of AZA should be reconsidered if good biomarkers that predict its efficacy are discovered. The response rate to AZA was moderately higher in MDS patients with TET2 mutations than in those without the mutations. Recently, increasing attention has been paid to a report, according to which, majority of the patients with TP53 mutations showed good response to a higher dose of decitabine. The use of AZA and the biomarkers predicting its efficacy is discussed.