Targeting systemic and tumor metabolic balances with ketogenic diets enhance efficacy of therapy in FLT3-ITD acute myeloid leukemia - PubMed
5 hours ago
- #metabolic targeting
- #ketogenic diet
- #AML therapy
- FLT3 mutations in AML are linked to poor prognosis, and FLT3 inhibitors (FLT3i) face resistance from lipid metabolism adaptations.
- A ketogenic diet (KD), either lard- or plant-based, improved FLT3i efficacy in mouse models, reducing tumor burden and engraftment by twofold.
- KD increased ketone bodies and lipid accumulation in plasma, liver, and AML cells, and created a PUFA:MUFA imbalance.
- The diet altered pentose, hexose, and amino acid metabolism, boosting sugar phosphates and vitamins in the host.
- Mechanistically, KD redirected anabolism to fatty acid oxidation and glycine-utilizing pathways, modulated FLT3 signaling, and promoted tumor cell differentiation, reducing FLT3i resistance.