Identification of drug targets against HSPC-like blasts. (A) Schema for in silico drug screening. DEG 1: DEGs from comparison between HSPC-like and lineage-like blasts; DEG 2: DEGs from comparison between HSPC-like blasts and normal HSPCs. (B-D) Scatterplots showing the log₂FC of DEGs based on scRNA-seq data in this study for AML (B), B-ALL (C), and T-ALL (D). (E) Overall scores of top 30 genes with known drugs based on the in silico screening. The type of supporting evidence is color-coded. (F) DepMap essentiality scores for BCL2, FLT3, and PIK3R1 in leukemia cell lines and nonleukemia cell lines, respectively. P values were computed using the Student t test. (G) Dot plot of association between subpopulation frequencies and IC₅₀ values. The color of the dots represents regression coefficients and the size of the dots represents the –log₁₀(adjusted P value of regression coefficient). The frequencies of HSPC-like and lineage-like blasts were computed using CIBERSORT. LC50 data and corresponding bulk RNA-seq data sets were downloaded from Lee et al.³⁹ P values were computed using the Student t test and adjusted for multiple testing using the Benjamini-Hochberg method. Significant associations are highlighted with circles with thicker borders. (H) Drug response curves showing the different response to FLT3i (sorafenib) and PI3Ki (buparlisib) between HSPC-like derived (n = 2) and lineage-like-derived (n = 2) PDX cells. DE, differentially expressed genes; IC₅₀, 50% inhibitory concentration;LC50, lethal concentration 50%; n.s., not significant; TTD, Therapeutic Target Database. The logos at the bottom of panel A are reused under Creative Commons licenses.