Inhibition of the succinyl dehydrogenase complex in acute myeloid leukemia leads to a lactate-fuelled respiratory metabolic vulnerability.

ABSTRACT: Metabolic programs can differ substantially across genetically distinct subtypes of acute myeloid leukemia (AML). These programs are not static entities but can change swiftly as a consequence of extracellular changes or in response to pathway-inhibiting drugs. Here, we uncover that AML patients with FLT3 internal tandem duplications (FLT3-ITD⁺) are characterized by a high expression of succinate-CoA ligases and high activity of mitochondrial electron transport chain (ETC) complex II, thereby driving high mitochondrial respiration activity linked to the Krebs cycle. While inhibition of ETC complex II enhances apoptosis in FLT3-ITD⁺ AML, cells also quickly adapt by importing lactate from the extracellular microenvironment. ¹³C₃-labelled lactate me

SUBMITTER: Erdem A 

PROVIDER: S-EPMC9018882 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature