BIRC5 supports the survival advantage of DNMT3A-mutant T-ALL cells. (A) GSEA plots showing significantly different gene sets in DNMT3A-mutant T-ALL specimens after 24-hour treatment with DEX + RUX (all downregulated after treatment). (B) Expression levels of genes within significantly different gene sets comparing WT DNMT3A and DNMT3A-mutant samples after 24 hours exposure to indicated treatments. (C) Principle component analysis of DMSO-treated control T-ALL gene expression profiles from patients with T-ALL by RNA sequencing. (D) Western blot showing DNMT3A levels in indicated T-ALL specimens. (E) Cell viability of wild-type DNMT3A (WT), DNMT3A-mutant–like (like) and DNMT3A-mutant (mut) T-ALL cells after 48 hours in vitro exposure to indicated drug combinations normalized to DMSO control for each patient sample. (F) Normalized expression level of BIRC5 in primary T-ALL cells after 24 hours exposure to indicated treatments. Individual patient specimens are denoted by the same color. (G) Western blot showing protein levels of BIRC5 in indicated samples from patients with T-ALL. (H) Western blot analysis of CUTTL1 cells after CRISPR/Cas9-mediated gene targeting of DNMT3A. (I) Western blot showing protein levels of BIRC5 in a representative WT DNMT3A T-ALL specimen after CRISPR/Cas9 targeting with indicated gRNAs. (J) Western blot for BIRC5 levels in specimens from patients with T-ALL after 48 hours treatment with indicated agents.