FLT3 TKIs synergize with ATRA to reduce proliferation of FLT3/ITD cells. (A-C) FLT3/ITD⁺ Molm14 cells were treated with (A) sorafenib (0-20 nM), (B) AC220 (0-10 nM), or (C) TTT-3002 (0-5 nM) either alone or in combination with ATRA (0-100 nM) for 48 hours, and cell proliferation was measured in quadruplicate by MTT assay. Error bars indicate average percentage OD ± SD. CI values were calculated by the Chou-Talalay method, shown at right. The dashed line designates a CI value of 1, with CI <1 being synergistic, CI = 1 being additive, and CI >1 being antagonistic. Data are representative of 3 independent experiments. (D) Viable leukemic blasts were isolated from FLT3/ITD⁺ AML patients and treated with sorafenib (20 nM) and/or ATRA (100 nM) in vitro. Viable cell counts measured by Trypan blue exclusion staining in triplicate at 72 hours. Error bars indicate average ± SD, and significant P values relative to combination treatment are shown (*P < .05, **P < .01, ***P < .001). OD, optical density.