Fig. 1: Arrest states of T-ALL subtypes in reference to human hematopoiesis.
a, Selection of n = 25 participants with ETP-ALL, n = 5 participants with near-ETP-ALL and n = 10 participants with non-ETP-ALL from the COG AALL0434 cohort (n = 1,411) based on response to induction therapy (day 29 MRD). b, UMAP representation of bulk RNA-seq data from n = 1,335 diagnostic T-ALL samples from COG AALL0434. Each point represents the bulk RNA-seq transcriptome for one participant. Participants selected for single-cell study are indicated by circular points. All participants with ETP are colored red. c, UMAP representation of CITE-seq (n = 271,603 cells) and scATAC-seq datasets (n = 332,663 cells; because of the size of the peak × cell matrix, 60,000 randomly downsampled cells are plotted). d, UMAP representation of healthy human hematopoiesis development reference trajectories, based on scRNA-seq (left; n = 49,623 cells) and scATAC-seq (right; n = 23,618 cells) data. The key stages of T cell development implicated are labeled. α/β, alpha–beta; γδ, gamma–delta. e, Arrest states of leukemic cells from 40 participants with T-ALL based on projection to healthy scRNA-seq (left) and scATAC-seq (right) reference. The D value from a two-sample Kolmogorov–Smirnov test is indicated to the side of brackets (*P < 2.2 × 10−16). Ten participants with T/M MPAL and ten participants with AML sequenced using identical assays are included as comparator groups (n = 60: ETP-ALL, 25; near-ETP-ALL, 5; non-ETP-ALL, 10; T/M MPAL, 10; AML, 10). f, Left, proportion of ETP blasts in four key T cell developmental stages, as compared to other participants with T-ALL. Right: proportion of ETP blasts in three key myeloid developmental stages, as compared to participants with T/M MPAL and AML. P values are based on a two-sided Mann–Whitney test. Results based on scRNA-seq projection are shown. The BMP stage encapsulates multipotent progenitors: HSPC, LMPP, CLP or ETP. The α/β stage encapsulates all cells that have moved past T cell commitment: DP, α/β, α/β (mature) or naive T. The box includes the median, hinges mark the 25th and 75th percentiles and whiskers extend 1.5 times the interquartile range (n = 60: ETP-ALL, 25; near-ETP-ALL, 5; non-ETP-ALL, 10; T/M MPAL, 10; AML, 10). Mono, monocyte; NK, natural killer.
