Fig. 1

Overview of molecular subtypes of T-ALL. (A) Overview of the T-ALL study workflow. RNA-seq data of T-ALL patients from eight cohorts are collected and integrated. After quality control, the gene-expression profile, sequence variations, and gene fusions identified from RNA-seq data are subjected to further analysis. tSNE analysis and hierarchical clustering methods are applied to determine the subtypes of T-ALL. (B) Two-dimensional tSNE plot and suprahexagonal map of 707 T-ALL patients. On the tSNE plot, each dot represents one T-ALL patient. The top 5% of genes demonstrating variance (with a perplexity score of 15 and a θ-value of 0.2) are subjected to tSNE analysis. Patient samples are colored according to the subtypes. Shown, Right, are illustrations of subtype-specific expression using a suprahexagonal map. (C) Bar plot of the percentage of patients based on age and gender in each subtype. (D) Profiling of clinical characteristics and genetic features identified in 707 T-ALL patients. Columns indicate T-ALL patients, and rows represent three panels: clinical information panel (subtypes, age, gender, clinical outcome, ETP status, T-cell maturation stage), fusion panel (gene fusions, including fusions reported in the original study from public cohorts and identified in RNA-seq), and expression panel (gene-expression level of dysregulated leukemic factors). Patient samples are ordered according to the unsupervised hierarchical clustering within each subtype. For the gene-expression panel, up- and down-regulated genes are shown in the heatmap in red and blue, respectively. Ten subtypes are defined according to their molecular features: G1 (LYL1/LMO2 overexpression, LYL1/LMO2), G2 (GATA-3 mutation, GATA-3 mut), G3 (SPI1-fusion, SPI1-fus), G4 (KMT2A-rearrangement, KMT2A-r), G5 (MLLT10-rearrangement, MLLT10-r), G6 (HOXA10-fusion, HOXA10-fus), G7 (TLX3 overexpression probably due to fusion to TCR, TLX3), G8 (TLX1 overexpression probably due to fusion to TCR, TLX1), G9 (NKX2-1 overexpression, NKX2-1), and G10 (TAL1/LMO1 overexpression, TAL1/LMO1).