While the interaction between polyamine metabolism and pan-cancer drivers including MYC, the RAS/RAF/MEK and the PI3K/AKT/mTOR pathways or tumor suppressors as p53 are established, future studies should address the interplay between the leukemia-specific molecular alterations and polyamine metabolism, aiding to biomarker-driven research for clinical translation. Here, AKT1 is linked to leukemia.