Why methylation is not a marker predictive of response to hypomethylating agents

摘要: The azanucleotides azacitidine and decitabine have been shown to induce hematologic response prolong survival in higher-risk myelodysplastic syndromes. They are inhibitors of DNA methyltransferase-1 DNA-hypomethylation. Induction apoptosis is also clinically relevant, particular during the first treatment cycles, when cytopenia a frequent side-effect. Since hypomethylating effect reversible, malignant clone has persist most responding patients, several cycles necessary achieve maintain responses, while interruption associated with rapid relapse. Methylation studies global gene-specific hypermethylation syndromes, but there seems be little relation between degree demethylation following response. presence concurrent genomic hypomethylation may impair predictive power current detection techniques. This scenario complicated by identification epigenetic enzyme mutations, including TET2, IDH1/2, DNMT3A EZH2, which important for treatment. Changes azanucleotide metabolism genes play role. In future, methylation analysis concentrating not only on promoters, gene bodies intergenic regions, identify key patients highest probability allow patient-tailored approach.