Survival advantage with inhibitor monotherapy and combination inhibitor treatment. Animals engrafted with (A) relapsed (ALL121) or de novo (JH331) CRLF2/JAK-mutant Ph-like ALL were treated with vehicle, ruxolitinib chow, gedatolisib 10 mg/kg intraperitoneally daily, or both ruxolitinib and gedatolisib until moribund (n = 5 mice per treatment cohort) for up to 120 days. Similarly, animals engrafted with (B) de novo ABL1-mutant ALL (NH011, PHL3) were treated with vehicle, dasatinib 10 mg/kg twice daily via oral gavage, gedatolisib, or both dasatinib and gedatolisib for up to 120 days. X-axes depict duration of inhibitor treatment (week 0 = treatment initiation) in mice after documentation of human leukemia engraftment (≥5% ALL in peripheral blood). Kaplan-Meier survival curves for each xenograft model were compared statistically using the log-rank test (P values indicated on graphs for each model). Dotted lines delineate median survival in each study with corresponding values for listed each treatment (black numbers). NR, 50% survival not reached.