Fig. 8: Distinct leukemia transcriptional signatures are linked to patient outcome.
a Heatmap of scaled normalized RNA expression of top 15 genes differentially expressed in leukemia cells of group 1 T-ALL patients and group 2 T-ALL patients. A score for each group was computed based on the sum of expression of these genes. b Violin plots showing surface protein expression of genes present in the T-ALL transcriptomic scores shown in (a) for malignant cells from T-ALL group 1 (n = 4 (BM), n = 6 (PB)) and T-ALL group 2 (n = 1 (BM), n = 4 (PB)) patients (downsampled to 300 cells/sample) at diagnosis. An unpaired t-test was used for statistical analysis; n.s.: not significant. c Group 2 scores for primary T-ALL patient samples of an independent dataset (GSE18115744) split by percentage of CD4-CD8-CD7- T cells analyzed by flow cytometry ( < 3% n = 11, >3% n = 3, see Supplementary Fig. 8b). A Wilcoxon rank-sum test was used for statistical analysis. d Visualization of T-ALL oncogenic groups ordered by group 2 scores for patient samples from the TARGET cohort (n = 265). A chi-square test comparing lower tertile and upper tertile was used for statistical analysis. e Kaplan-Meier curve of event-free survival (EFS, n = 580) and overall survival (OS, n = 597) of MRD low T-ALL patients from the Gabriella Miller Kids First Pediatric Research Program dbGaP phs002276.v2.p1 grouped based on score for group 2. A log-rank test was used for statistical analysis to compare high versus low score groups, also see Supplementary Fig. 8c. f Illustration of the remodeled immune system and leukemic Rap1 signaling in group 2 T-ALL patients.
