Different methylation in normal progenitors and AML. (A) Two-way unsupervised hierarchical analysis (Pearson correlation, complete clustering) of differentially methylated CpG residues (n = 2764) between CN-AML and myeloid progenitor cells. Each column represents a sample and each row a CpG site. CpG sites are divided into 4 major DMCs, which are color-coded: red represents DMC 1; blue, DMC 2; green, DMC 3; and purple, DMC 4. (B) An average plot showing differentially methylated CpGs. Each autosomal CpG residue is represented with its average β-value for myeloid progenitors on the y-axis, and the corresponding average β-value of all CN-AML samples on the x-axis. Color codes mark the clustered CpGs defined in Figure 3A, and beige dots represent nondifferentially methylated CpG residues. (C) Principal components analysis of the differentially methylated CpG sites shows separation of the DMC 1 + DMC 2 from DMC 3 + DMC 4, whereas only z-axis differences separate DMC 1 from DMC 2 and DMC 3 from DMC 4. (D) The DMCs have significantly different percentages of CpG sites within CpG islands shown here in a Venn diagram. On the whole array, 72.5% of CpG sites are within CpG islands. (E) Scatterplot showing the average β-values of the differentially methylated genes on the y-axis for all CN-AML samples (blue) and the myeloid progenitors from normal bone marrow (green), highlighting the variability among AML samples who have increased average β-values compared with the normal controls (P = .0003).