Amino Acid Metabolic Vulnerabilities in Acute and Chronic Myeloid Leukemias

Amino acid (AA) metabolism plays an important role in many cellular processes including energy production, immune function, and purine and pyrimidine synthesis. Cancer cells therefore require increased AA uptake and undergo metabolic reprogramming to satisfy the energy demand associated with their rapid proliferation. Like many other cancers, myeloid leukemias are vulnerable to specific therapeutic strategies targeting metabolic dependencies. Herein, our review provides a comprehensive overview and TCGA data analysis of biosynthetic enzymes required for non-essential AA synthesis and their dysregulation in myeloid leukemias. Furthermore, we discuss the role of the general control nonderepressible 2 (GCN2) and-mammalian target of rapamycin (mTOR) pathways of AA sensing on metabolic vulnerability and drug resistance.

Automated summary

The metabolism of amino acids plays a crucial role in cellular processes, especially in cancer cells that require increased amino acid uptake for energy production. This review focuses on the dysregulation of biosynthetic enzymes in myeloid leukemias and the impact of GCN2 and mTOR pathways on metabolic vulnerability and drug resistance.