DNMT3A mutations in T-ALL convey a survival benefit and chemotherapy resistance. (A) Western blot of freshly isolated control (Ctl) and Dnmt3a^KO (3aKO) NICD-expressing T-ALL cells. (B) Western blot of primary human T-ALL cells showing expression of antiapoptotic proteins. (C) Cell viability of primary human T-ALL cells after 48 hours in vitro exposure to indicated chemotherapeutics normalized to DMSO control for each patient sample. (D) Representative flow cytometry plots showing annexin-V staining of T-ALL cells after exposure to DEX with/without RUX. (E) Cumulative cell viability of DNMT3A wild-type (WT) and mutant (mut) T-ALL cells after 48 hours in vitro exposure to indicated drug combinations normalized to DMSO control for each patient sample. (F) Kaplan-Meier plots of representative DNMT3A WT (UPN 1229314) and DNMT3A mutant (UPN K424) T-ALL specimens xenografted into NOD-scid IL2Rgamma^null (NSG) mice and then treated with indicated agents once T-ALL burden reached 10% of the peripheral blood.