Targeting polyamine metabolism and eIF5A hypusination in pediatric acute myeloid leukemia

Therefore, there is an urgent need to develop novel therapies for pediatric AML patients. Numerous studies have demonstrated that cellular metabolism is a key vulnerability in adult AML; however, we understand very little about metabolism in pediatric AML.

Using pediatric AML patient derived xenograft models, we demonstrate that polyamine metabolism is a pharmacologically targetable vulnerability of pediatric AML cells. Further, depletion of polyamines sensitizes pediatric AML cells to chemotherapy in vitro and in vivo. Mechanistically, polyamine depletion causes reduced protein synthesis through decreased hypusination of translational elongation factor eIF5A.