Core transcriptional regulatory circuitries of HSPC-like blasts. (A) Heat map showing enriched gene ontology terms of each regulon in the shared TRN (see “Methods”). Shades of blue represent –log₁₀(enrichment P value). Selected terms are labeled. (B) Bar plots showing the numbers of shared and leukemia subtype–specific targets of each core TF. (C) Box plots showing log₂ expression fold-change of shared and subtype-specific targets. Red dashed lines indicate log₂FC = 0. (D) Core HSPC-like TRN shared across leukemia subtypes. All TFs and targets are shared across leukemia subtypes. Node color represents average log₂FC between HSPC-like and lineage-like blasts across leukemia subtypes. (E) Enriched gene ontology terms of shared targets. (F) Core TRN signature in baseline and in silico TF KO matrices in AML HSPC-like blasts using scRNA-seq in this study (B-ALL results in supplemental Figure 9C; T-ALL results in supplemental Figure 9D). The colored boxes represent baseline signatures; gray boxes represent in silico TF KO signatures. P values were computed using the Student t test. (G) Core TRN signature in paired pediatric T-ALL bulk RNA-seq data set from X01.¹⁹ P values were computed using a paired t test. (H) Core TRN signature for the PDX treatment scRNA-seq data set in this study. P values were computed using the 2-sided Student t test. (I) Core TRN signature stratifies MRD level in the bulk RNA-seq cohort. Each cohort was classified as induction failure (≥5%), MRD5 (≥1% and <5%), MRD1 (≥0.01%), and MRD⁻ on the basis of day 29 MRD level at the EOI. The source of AML and B-ALL cohorts: TARGET; the source of 2 T-ALL cohorts: X01 and TARGET. P values were computed using the Student t test and indicated on the top of each box plot. Red dashed lines indicate a TRN score of 0 on the y-axis. (J) TRN signature stratifies patient survival across leukemia subtypes. The source of patient cohort data is 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 as covariates. Dex, dexamethasone; IF, induction failure; KO, knockout; OS, overall survival; TNF, tumor necrosis factor; TRN, transcriptional regulatory network; Vinc, vincristine.