Fig. 6: Impact of epigenetic regulators on global and CGI methylation in ALL.

a, Correlation of CGI and global mean methylation with DNMT3B expression across patients with T-ALL, Ph-like and DUX4/ERG (n = 27, 7 and 12 patients, respectively). Correlation was calculated using a two-sided Spearman correlation test (rho, Spearman correlation) and P values were adjusted for multiple testing correction using false discovery rate (FDR) (Padj, adjusted P value). b, Heatmap showing the methylation status of the promoter CGIs of a panel of epigenetic regulators associated directly and indirectly with DNA methylation. Only ARID1B does not have a promoter CGI and instead the mean methylation of the promoter region is shown (1.5 kb upstream and 500 bp downstream of the TSS). SUV39H1 is located on the X chromosome, which is excluded from methylation analysis due to the difference in methylation between female and male samples (inactivated allele is fully methylated in females). c, Correlation of TET2 (top) and WT1 (bottom) promoter methylation with mean CGI (left) and global methylation (right) levels across patients with T-ALL, Ph-like and DUX4/ERG with precursor B and T cells as control (n = 27, 7, 12, 4 and 2 samples, respectively). A subset of patients with T-ALL^IM and T-ALL^HM shows hypermethylation of the TET2 and/or WT1 promoter accompanied by increased average CGI and global methylation levels. WT1 promoter hypermethylation is largely mutually exclusive with WT1 mutations.