Exploiting leucine metabolism for therapeutic benefit in acute Myeloid Leukemia

Abstract

Acute Myeloid Leukemia (AML) presents significant challenges in treatment, especially for elderly patients. Conventional therapies have limitations, necessitating the exploration of novel strategies. Metabolic reprogramming in cancer cells offers promise in this regard, with growing evidence pointing to dysregulated leucine metabolism in AML. Leucine deprivation has shown potential in inhibiting leukemic cell proliferation, inducing cell cycle arrest, and enhancing differentiation. Combination therapies involving leucine deprivation and chemotherapy have exhibited synergistic effects. The precise molecular mechanisms of leucine deprivation's anti-leukemic effects, particularly its potential impact on the mTOR signaling pathway, require further elucidation. Targeting BCAAs and other amino acids, such as methionine and lysine, holds promise in disrupting leukemia cell proliferation and promoting apoptosis. These findings underscore the potential of exploiting leucine metabolism and amino acid pathways for therapeutic benefits in AML.