Fig. 1: The ALL genome is unusually highly methylated.

a, Cohort overview including all examined ALL subtypes with age information (P, pediatric aged 0–15 years; AYA, adolescents and young adults aged 16–39 years; A, adults aged ≥40 years). Healthy cells were purified by fluorescence-activated cell sorting from bone marrow of children without leukemia and neonatal thymi. b, Genome browser tracks for WGBS data of representative memory B cells, healthy colon tissue, precursor T cells, chronic lymphocytic leukemia (CLL), colon adenocarcinoma (COAD) and T-ALL for an exemplary locus (ACER1 and neighboring genes; chr19:6,282,123–6,425,048). CLL and COAD display the characteristic global loss of methylation in comparison to their respective healthy tissue, whereas T-ALL methylation remains more highly methylated and comparable to precursor T cells. c, Correlation of CpG methylation levels between memory B cells and CLL, healthy colon and COAD as well as precursor T cells and T-ALL (blue, low density; red, high density, same samples as in b). Black lines mark the difference of 0.1 from the diagonal in both directions. d, Global methylation levels averaged across all covered CpGs outside of CGIs (CpGs in CGIs are excluded to not bias global quantifications by potential differences in CpG-dense regions) per sample for ALL subtypes, other hematopoietic malignancies from Blueprint and solid tumors from TCGA (left) as well as healthy cell types of the lymphoid lineages from this study and Blueprint (right) (Supplementary Tables 2 and 3). Lines denote the median, edges denote the interquartile range (IQR), whiskers denote 1.5 × IQR and minima/maxima are represented by dots. The number of independent samples is indicated at the top. Blueprint cancer types include acute myeloid leukemia (AML), T-cell prolymphocytic leukemia (TPLL), CLL and mantle cell lymphoma (MCL). TCGA tumor types include bladder urothelial carcinoma (BLCA), breast invasive carcinoma (BRCA), COAD, lung adenocarcinoma (LUAD), lung squamous cell carcinoma (LUSC), rectum adenocarcinoma (READ), stomach adenocarcinoma (STAD) and uterine corpus endometrial carcinoma (UCEC). T-ALL and AML show global DNA methylation levels comparable to hematopoietic control cells, whereas B-ALL subtypes show a mild loss not comparable to the drastic loss of other tumor types. DP, double positive; SP, single positive.