Early-phase therapies, including p53 reactivators and multi-kinase inhibitors, show preclinical promise but lack definitive clinical efficacy to date.<h4>Conclusions</h4>Targeted therapies have improved outcomes in molecularly defined subsets of AML, with menin, <i>IDH</i> and <i>FLT3</i> inhibitors representing major advances. Here, TP53 is linked to acute myeloid leukemia.