High levels of CD117 and CD82 gene expression demarcates an early stage subgroup, enriched in MRD of human T-ALL. (A) Fraction of MRD 29 days after the start of therapy in 252 patients with T-ALL from the COG TARGET study.⁵⁰ All patients have been subdivided in CD117^lowCD82^low (n = 146), CD117^highCD82^low (n = 42), CD117^lowCD82^high (n = 44), and CD117^highCD82^high (n = 20) groups based on the highest 25th percentile of transcriptional level of CD117 and CD82 genes on RNA-seq data of each patient with T-ALL. ∗P < .05, ∗∗P < .01, ∗∗∗P < .001 (2-way analysis of variance). (B) tSNE plot of RNA-seq data from 252 patients with T-ALL (COG TARGET study).⁵⁰ Each sample derived from the CD117^highCD82^high subgroup is indicated by red dot. Early T-cell precursor ALL are also highlighted by the red contour plot. Correlation between CD117/CD82 subgroups and early T-cell precursor ALL (C), precortical stage (D), or transcription factor/genetic subgroups (E) among 252 patients with T-ALL. Statistical P values were calculated by Fisher exact test, corrected for multiple comparisons by FDR using a 2-stage linear step-up procedure of Benjamini, Krieger, and Yekutieli. (F-G) Gene set enrichment analysis. (F) The gene signature was derived by the differential expression analysis of integrated RNA-seq and ChIP-seq data sets from FOXO3^null CTNNB1^null PF382 cells cotransduced with FOXO3-TM and β-catenin (ΔGSK) vs other conditions (n = 140 genes). (G) The gene list derives from the differential expression analysis of scRNA-seq data from 3 highlighted CD117^highCD82^high Phenograph clusters vs the others (n = 185 genes). All genes were ranked for differential expression in CD117^highCD82^high vs the rest of the patients with T-ALL from the COG TARGET study.⁵⁰