Beyond novel agents either targeting abnormal cell transport of NPM1-mutated protein, such as XPO1 inhibitors, or targeting HOX expression, namely the menin-MLL inhibitors MI3454 and VTP-50469, or triggering nucleolar stress, such as dactinomycin, which have shown anti-leukemic activity in pre-clinical models and have started to be investigated in humans, immunotherapeutic approaches targeting NPM1-mutated protein processed and presented by HLA system on AML cell surface could represent an effective treatment option, at least in some distinct disease phases [7,91,92]. The gene discussed is KMT2A; the disease is acute myeloid leukemia.