These results demonstrate that the combination of Mcl-1 inhibition and FLT3 inhibition shows promising antileukemic activities against AML cells resistant to chemotherapy, and that the suppression of c-Myc through the JAK2/STAT5 pathway by FLT3 inhibition plays an important role in the mechanism of action of combined Mcl-1 inhibition with AZD5991 and FLT3 inhibition with gilteritinib or MRX-2843. Here, FLT3 is linked to acute myeloid leukemia.