Kojima, et al. demonstrated that the simultaneous inhibition of PI3K/Akt/mTOR axis and of MDM2 induced the dephosphorylation of 4E-BP1, a decrease in MDM2, p21, Noxa, and Bcl-2 expression, and the conformational change of Bax, thus affecting mitochondrial stability and enhancing p53-mediated mitochondrial apoptosis in p53 wild-type AML [58]. Here, MDM2 is linked to acute myeloid leukemia.