Figure 4: The LSC epigenetic signature is associated with overall survival in human AML.

(a) TCGA samples were classified as LSC like or Blast like based on DNA methylation alone by generating methylation profiles of the LSC and Blast populations, and then calculating scores of each sample based on the probability of being closer to either LSC or Blast. Kaplan–Meier survival analysis was then applied to these groups as indicated. Statistical significance was determined by the log-rank test (n=192; 93 LSC-like and 99 Blast-like patients). (b–e) Expression of the LSC epigenetic signature genes was combined to create an LSC score, which was then calculated in AML samples. The first principal component of genes in the LSC signature was computed, and patients were stratified as ‘high’ or ‘low’ relative to its median value in four independent cohorts including TCGA (n=182; 91 high-score and 91 low-score patients), (b) Metzeler et al. (n=163; 81 high-score and 82 low-score patients) (c), Wouters et al. (n=262; 131 high-score and 131 low-score patients) (d) and Wilson et al. (n=169, 84 high-score and 85 low-score patients) (e). In each cohort, patients were classified into high and low groups based on the median value. Kaplan–Meier survival analysis was then applied to these groups as indicated. Statistical significance was determined by the log-rank test.