Expressers highly sensitive to ruxolitinib are characterized by broad H3K4me3 domains on the IL-7R promoter. (A) Gene set variation analysis between T-ALL^IL7R-/low (n = 26), T-ALL^IL7R+/WT (n = 28), and T-ALL^Mut (n = 42) using a custom IL-7R pathway gene set of 36 genes selected from reactome (REACTOME_INTERLEUKIN_7_SIGNALING) and biocarta (BIOCARTA_IL7_PATHWAY) databases. Box plots show lower, median, and upper quartiles. Whiskers mark the 10^th and 90^th percentiles. Dots represent outliers. Kruskal-Wallis test with post hoc Dunn multiple comparisons test. ∗P < .05; ∗∗P < .01. (B) IL-7R was evaluated using a multiomic approach combining EPIC-array, CHIP-seq, and bulk RNA-seq on 10 T-ALL^IL7R−/low, 9 T-ALL^IL7R+/WT, and 7 T-ALL^Mut. The heatmap shows the level of CpG-DNA methylation (dna_meth) and H3K4me3 breadth (H3K4me3_promoter) on IL-7R promoter/transcription starting site as well as the IL-7R transcript level for each sample. Samples are classified by k-means (k = 3), then hierarchical clustering. For each metric, values were centered and reduced. (C) H3K4me3 tracks on IL7R promoter for 15 T-ALL^IL7R+/WT, 8 T-ALL^Mut, and 15 T-ALL^IL7R−/low. (D) Box plots showing the breadth (bp) of H3K4me3 peaks on IL-7R transcription starting site for the same T-ALL as in panel C, based on the 3 categories defined in this article (left) or their phenotype (right). Mann-Whitney test. The P-value is indicated for each comparison. (E) Correlation between sIL-7R expression (percentage of CD127⁺ blasts) and H3K4me3 peak quantile–normalized coverage signal on the IL-7R promoter. The dashed line indicates the threshold for CD127 positivity (20%). Correlation curve and 95% confidence interval are shown. Pearson correlation test. (F) Inverse correlation between ruxolitinib sensitivity (log2 IC₅₀) and H3K4me3 peak signal on the IL-7R promoter. Correlation curve and 95% confidence interval are shown. Pearson correlation test.