Abstract 3270: Leukemia induced cachexia is driven by dysregulated tryptophan metabolism resulting in inhibition of muscle regenerative capacity

Key Points

• To define the mechanisms driving leukemia-induced muscle atrophy, focusing on metabolic dysregulation and its effects on muscle regeneration.
• Used a syngeneic acute myeloid leukemia mouse model.
• Analyzed muscle mass and structure via H&E staining and RNA sequencing.
• Examined satellite cell activation using a Pax7-CreERT2 reporter mouse model.
• Performed NMR analysis on serum to assess amino acid levels and metabolites.
• Conducted cytokine profiling to evaluate atrophy-associated mediators.
• Tumor-bearing mice exhibited significant weight loss and reduced gastrocnemius mass.
• RNA seq indicated increased expression of atrophy genes TRIM63 and FBXO32 linked to muscle loss.
• Despite normal satellite cell numbers, muscle showed impaired regenerative capacity with absent centrally located nuclei.
• Serum analysis revealed elevated kynurenine pathway metabolites linked to oxidative stress.
• Cytokine profiling showed elevated levels of atrophy-associated mediators, particularly IL17A.