Clustering of DNA methylation profiles according to FLT3-ITD. (A) hierarchical clustering analysis with the methylation levels of the 1243 CpG sites with methylation differences of ≥20% generated 3 clusters (A, B, and C), and associations of the DNA methylation cluster according to FLT3-ITD status with mutations, expression levels, cytogenetic features, and outcomes in pediatric patients with AML. DNA methylation levels were classified into 3 groups according to their β value: hypermethylation (≥0.67), intermediate methylation (0.34-0.66), and hypomethylation (≤0.33), respectively. Light blue, orange, and dark orange indicate presence of the specified mutation, high gene expression, and chromosomal aberration, respectively. Brown indicates KMT2A-MLLT3 fusion, and dark blue indicates FLT3-ITD with high allele ratio (>0.7). Gray and black indicate non–complete remission (CR) and events and deaths, respectively. (B-C) Comparison of the Kaplan-Meier curves of OS (B) and EFS (C) between clusters A and B or C of panel A in 15 patients with FLT3-ITD. (D) Gene ontology (GO) biologic process for the top 1243 CpG-related 1481 genes. FDR, false discovery rate; GO, gene ontology; KMT2A-R, KMT2A rearrangement; PTD, partial tandem duplication.