Cotreatment with TQ and ruxolitinib or BET inhibitor OTX015 reduced spleen size and significantly improved survival of NSG mice bearing PDX models of post-MPN sAML. (A) NSG mice were infused with luciferized HEL92.1.7 cells and treated with TQ (30 mg/kg, daily, orally [gavage]) for 4 weeks. The survival of the mice is shown as a Kaplan-Meier survival plot. Significance was calculated by a Mantel-Cox log-rank test. ∗P < .05. (B) Kaplan-Meier survival plot of NSG mice (n = 6 per cohort) infused with a mutant CALR sAML PDX (CALR-E381 deletion, TERT A1062T mutation) and treated with vehicle or the indicated doses of TQ for 8 weeks. Significance was calculated by a Mantel-Cox log-rank test. (C) Spleen lengths of NSG mice infused with a mutant CALR sAML PDX and treated with vehicle, TQ and/or ruxolitinib, or OTX015 for 6 weeks. ∗P < .05; ∗∗P < .01. (D) Representative spleen images from panel C. (E) Kaplan-Meier survival plot of NSG mice infused with a mutant CALR sAML PDX (CALR-E381 deletion, TERT A1062T mutation) and treated with vehicle, the indicated doses of TQ and/or ruxolitinib, or OTX015 for 10 weeks. Significance was calculated by a Mantel-Cox log-rank test. ∗P < .05; ∗∗∗P < .005; ∗∗∗∗P < .001. GFP, green fluorescent protein; Luc, luciferase; mtCALR, mutant CALR; mtTERT, mutant TERT; RUX, Ruxolitinib; Rx, treatment.