(A) WT C57Bl/6 mice were engrafted with Arf−/− BCR-ABL1 MIG-IK6 or MIG cells and randomized to vehicle, bex and/or dasatinib. On Kaplan-Meier analysis, bexarotene significantly increased survival time, with the greatest effect observed in mice treated with both drugs. **p<0.005, *p<0.05; n=5 mice per group. (B) Dose-response curves of human BCR-ABL1 CDKN2A/B-deleted (i.e., INK4/ARF−/−), IKZF1 Δ4-7 (IK6), IK6 + R502W mutation, or IK6 + Δ2-7 leukemic cells harvested from NSG mice and immediately treated ex vivo with increasing concentrations of bexarotene (Bex), or all-trans-retinoic acid (ATRA) at increasing concentrations of dasatinib. Each retinoid inhibited cell proliferation, even at very low concentrations of dasatinib, and reduced the TKI IC50. n=3 biological replicates performed in triplicate. (C) schematic summarizing effects of IKZF1 alterations and their reversal by retinoids.
See also Figure S5.