NPM1 and acute myeloid leukemia: While older unfit patients affected with NPM1-mutated AML rarely show long-term response to single HMAs, the combination of BCL-2 inhibitor venetoclax with HMAs, preferably 5-azacitidine, is currently emerging as the standard of care in this clinical setting, inducing CR in 70–90% of cases and significant survival advantages compared to alternative therapeutic strategies [7,8,76,77,78].