HSPC-like blast transcriptomic signatures predict clinical outcome. (A) Heat maps of DEGs between HSPC-like and lineage-like blasts across leukemia subtypes: upregulated genes in HSPC-like blasts in at least 1 subtype (left); downregulated genes in HSPC-like blasts in at least 1 subtype (right). DEGs were determined by abs(log₂[FC]) > 0.25 and adjusted P value < .05. DEGs were pooled and clustered by k-means clustering (k = 9 for left panel, k = 5 for right panel) on the basis of their log₂FC. The full list of DEGs is provided in supplemental Table 5. (B) Heat map showing enriched gene ontology terms of each DEG cluster in panel A. Shades of blue represent the –log₁₀(enrichment P value). Selected terms are labeled. (C) Single-cell RNA-seq–derived HSPC-like signatures can stratify MRD levels in bulk RNA-seq cohort. Rows, leukemia subtypes; columns, single-cell derived signatures. The AML cohort was divided into induction failure (MRD > 5%), MRD5 (5% ≥ MRD > 1%), MRD1 (1% ≥ MRD > 0.1%), and MRD⁻ (MRD ≤ 0.1%); B-ALL and T-ALL cohorts were divided into induction failure (MRD > 5%), MRD5 (5% ≥ MRD > 1%), MRD1 (1% ≥ MRD > 0.01%), and MRD- (MRD ≤ 0.01%) on the basis of their day 29 MRD level at the EOI. Dashed boxes highlight the comparison that related to each signature. Sample numbers for each group were indicated. P values were computed using the 2-sided Student t test. The source of AML and B-ALL cohorts: TARGET; T-ALL cohort: AALL0434. (D-F) Pan-HSPC-like signature can stratify patient survival across leukemia subtypes. The source of patient cohort data and case numbers are indicated at the top of each plot. The P values were calculated using the log-likelihood statistic from the Cox proportional hazards test with central nervous system status and white blood cell count included as covariates. BCR, B-cell receptor; OS, overall survival; TCR, T-cell receptor.