This study is the first to demonstrate that the USP14/UCHL5 inhibitors b-AP15 and AUR effectively inhibit the K48-mediated deubiquitination of ubiquitin bound to FLT3, resulting in FLT3 downregulation and inhibition of its downstream signaling in FLT3-ITD-positive AML cells. This evidence concerns the gene FLT3 and acute myeloid leukemia.