Aberrant promoter methylation correlates with disease evolution. (A) Patients with RAEB/AML show a higher average and median methylation (β-value; P = .001) and a higher number of aberrantly methylated sites (P < .001) than those with low-risk MDS (aberrant methylation was defined as a methylation β-value for a CpG site that was significantly greater (P < .001) than the methylation β-value for the corresponding site in the group of normal bone marrow controls). The number of aberrantly methylated CpG sites in patients with complex cytogenetic abnormalities (defined as 3 or more abnormalities by standard metaphase karyotyping) is significantly higher (P = .05) than in patients without complex cytogenetic abnormalities; however, the average methylation level (β-value) was not significantly different (P = .23). Each dot represents the average array methylation level in a patient; the horizontal dashed line indicates the mean value for the patient group. Numbers below the graph represent the average number of aberrantly methylated CpG sites (of 1505 sites analyzed) in each patient group. Normal indicates normal whole bone marrow; CD34⁺ are normal CD34⁺ selected hematopoietic cells. (B) The number of concordantly hypermethylated sites by patient group, defined as CpG loci that were aberrantly methylated in more than 50% of patients with RAEB/AML, low-risk MDS, and CMML, respectively. Each circle represents a patient group, and the overlapping areas represent common aberrantly methylated genes. (C) CpG sites that became hypermethylated during evolution of RA to RCMD. Each dot represents a CpG site. The hypermethylated CpG sites are listed. (D,E) Concordantly hypermethylated loci in patients with low-risk MDS and RAEB/AML, respectively. Each dot represents a CpG site. Genes shown more than once represent those with more than one hypermethylated loci. The percentage refers to the proportion of patients with aberrant methylation at the specified locus.