<i>Results and Conclusions</i>: In the present review article, we summarize our current understanding of the biology of <i>KMT2A-r</i> in AML development and the recent consistent progress made in the treatment of <i>KMT2A-r</i> AML through new chemotherapy regimens and targeted therapy using Menin inhibitors. Here, MEN1 is linked to acute myeloid leukemia.