We study the molecular mechanisms involved in the survival and proliferation of acute myeloid leukemia. FLT3 inhibitors, such as midostaurin, gilteritinib and quizartinib, are newly approved therapeutic agents for acute myeloid leukemia and have shown significant benefits in controlling tumor growth in clinical trials. However, drug resistances, which involve several acquired FLT3 gene mutations, were observed in the studies. To overcome the resistance, we investigated the molecular mechanisms underlying the resistances and found that HSP90 inhibition promotes the lysosomal protein degradation of mutant FLT3. We are currently analyzing the survival and proliferation mechanisms in several acute myeloid leukemia cells that possess various gene mutations, including FLT3 resistant mutations.