Cotreatment with TQ and BET inhibitor OTX015 reduced leukemia burden greater than either agent alone in a murine BM transplant model. (A) Murine JAK2-V617F, TP53-KO cells were treated with the indicated concentrations of TQ for 96 hours. At the end of treatment, relative cell viability was determined using a CellTiter-Glo assay. The percentage of viable cells in each condition was normalized relative to the untreated control cells. All the data points from 2 independent experiments performed in triplicate are shown; bar, median loss of viability. ∗P < .05; ∗∗∗P < .005. (B) JAXBOY mice were infused with 1 × 103 murine JAK2-V617F, TP53-KO cells plus 1 × 106 total BM cells from JAXBOY donor mice. Mice were treated with the indicated doses of TQ and/or OTX015 for 2 weeks. The mice were euthanized, and the spleen and BM cells were collected. The isolated cells were analyzed for dTomato fluorescence by flow cytometry. ∗P < .05; ∗∗∗P < .005; ∗∗∗∗P < .001. (C-E) C57/BL6 mice (n = 5 mice per cohort) were treated with vehicle or TQ for 2 weeks. Mice were bled and complete blood counts (CBCs) were performed. The mice were allowed to recover with no treatment for 2 weeks and then bled for CBC analysis. ∗P < .05, compared with vehicle-treated mice. ns, not significant; Rx, treatment; WBCs, white blood cells.
