dlvr.it
Translational control of leukemic metabolism and disease progression
Acute myeloid leukemia (AML) is an aggressive hematological cancer with a 70% five-year mortality rate. Relapse occurs in approximately half of adults treated with intensive chemotherapy, while responses to targeted therapies are short-lasting. Frequent mutations in signaling pathways, such as FLT3 tyrosine kinase and RAS, lead to dysregulated mammalian target of rapamycin complex 1 (mTORC1)and mitogen-activated protein kinase (MAPK) signaling, increased protein synthesis, enhanced mitochondrial fitness, and metabolic adaptations that drive leukemic cell proliferation and survival. Here, emerging evidence supporting the unique role of eukaryotic initiation factor 4F as a key driver of the expression of proteins regulating leukemic cell metabolism and survival and the potential therapeutic benefit of targeting this pathway pharmacologically in AML are discussed.