The effect of AC220 and CCT241736 on cell viability of quizartinib-resistant primary AML cells. (A-C) Primary AML cells were collected from 3 patients with quizartinib-resistant AML (AML-7, AML-14, and AML-15). The AML cells were collected after clinical quizartinib resistance had emerged at the point of relapse. Cells were cocultured in triplicate with irradiated MS-5 at a density of 1.2 million cells per milliliter and were treated with either DMSO control, AC220 (left graphs), or CCT241736 (right graphs) at the indicated doses. Three days after treatment, cells were harvested, and viable cells were counted using a Luna-II Automated Cell Counter. All experiments were done in triplicate and results were shown as mean ± SEM (*P < .05 compared with control). (D) Explanatory model: activated FLT3 induces the transcription of several downstream genes, including the Aurora B partner survivin, via STAT1, -3, and -5 proteins. Aurora A plays a role in centrosome maturation and spindle formation, whereas Aurora B regulates the spindle checkpoint in kinetochore microtubule attachment and cytokinesis. CCT241736 inhibits Aurora kinases and the FLT3 pathway in multiple steps. This inhibition leads to cytokinesis failure and inhibition of leukemic proliferation.