Inhibition of senescent stemlike subpopulations in Ph-like ALL. (Upper panel) Integrated transcriptomic, epigenomic, and phosphoproteomic analyses revealed dynamic shifts in MYC pathway and STAT5 phosphorylation (pSTAT5) during treatment with ruxolitinib. Dual inhibition of MYC and JAK/STAT5 pathway suppresses leukemia growth. (Lower panel) Single-cell sequencing of residual leukemic blasts post-TKI and BCL-2 inhibition identified a poor prognostic senescence-associated stem cell–like subpopulation regulated by AP-1, which is sensitive to dual JAK/STAT and BCL-2 inhibition. ATAC-seq, assay for transposase-accessible chromatin using sequencing; RNA-seq, whole transcriptome sequencing by RNA-sequencing.