FLT3 is mutated in roughly 30% of human AML. We used our model of APL with activated FLT3 to assess the effectiveness of chemotherapy in combination with SU11657, an inhibitor of FLT3. We found that median survival of untreated and doxorubicin-treated mice was not significantly different. While SU11657 alone increased median of survival to 55 days (P=0.01), dual therapy increased median survival to 62 days (P=0.003) when compared to controls. Neither agent alone or in combination increased survival of control mice. These results suggest that the use of targeted therapeutics can overcome resistance to traditional chemotherapies in AML.