BIRC5 as a precision medicine target for DNMT3A-mutant T-ALL. (A) Cell viability of indicated T-ALL specimens (normalized to negative control small interfering [siRNA]) 48 hours after nucleofection with BIRC5 siRNA. (B) Compiled normalized cell viability averaged for individual WT DNMT3A and DNMT3A-mutant T-ALL samples after nucleofection with BIRC5 siRNA. (C) Cell viability of indicated T-ALL specimens (normalized to DMSO control) after 48 hours exposure to YM155. (D) Compiled normalized cell viability averaged for individual WT DNMT3A and DNMT3A-mutant T-ALL samples after 48 hours exposure to YM155. (E) Kaplan-Meier plots of NSG mice xenografted with indicated T-ALL specimens after CRISPR/Cas9 genome targeting with indicated gRNAs. (F) VAF of CRISPR edits from indicated gRNAs in T-ALL blasts from peripheral blood (6-8 weeks after transplant) and BM of moribund mice (euthanized) normalized to initial targeting efficiency 48 hours after nucleofection (initial) at time of transplant.