Antileukemic efficacy of combination MEK and ATR inhibition in human MLL-AF4 mutant N-RAS B-ALL in PDX models. Patient samples harboring MLL-AF4 and mutant N-Ras were injected in NSG mice that were treated with vehicle, single-agent trametinib (1 mg/kg), single-agent AZ20 (50 mg/kg), or the combination for 15 days. Percentage of human leukemic blasts in hematopoietic tissues and spleen weights of treatment cohorts for PDX 83 (A) and PDX 24 (B). For all vehicle and single-agent treatment groups, n ≥ 4 mice; for the combination group, n = 3. ***P < .001, **P < .01, *P < .05.