HMAs in CMML. Mutations affecting key genes involved in epigenetic regulation lead to global hypermethylation in CMML. Genes targeted with loss-of-function (LOF) mutations are shown in orange and gain-of-function mutations (GOF) are in blue (upper left panel). Mutation frequencies are listed in red next to genes. Methylation marks affected are in blue (M) at histone 3 lysine 27 (K27) and yellow (M) on DNA. Low doses of 5-azacitidine and its deoxyribose form, decitabine, lead to re-expression of genes silenced by aberrant DNA methylation by preventing new strand methylation by DNA methyltransferases (upper right panel). Epigenetic HMA treatment responses are included (lower left panel). CpG, cytidine bound through a phosphate; 5-hmc, 5-hydroxymethylcytosine; 5-mc, 5-methylcytosine.