Nature Communications (Apr 2022)

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

  • Ayşegül Erdem,
  • Silvia Marin,
  • Diego A. Pereira-Martins,
  • Marjan Geugien,
  • Alan Cunningham,
  • Maurien G. Pruis,
  • Isabel Weinhäuser,
  • Albert Gerding,
  • Barbara M. Bakker,
  • Albertus T. J. Wierenga,
  • Eduardo M. Rego,
  • Gerwin Huls,
  • Marta Cascante,
  • Jan Jacob Schuringa

DOI
https://doi.org/10.1038/s41467-022-29639-0
Journal volume & issue
Vol. 13, no. 1
pp. 1 – 15

Abstract

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Inhibition of specific metabolic pathways often drives metabolic adaptation. Here, the authors show that FLT3-ITD + acute myeloid leukemia cells are OXPHOS-driven, and inhibition of complex II activity results in increased lactate influx to drive respiration, which creates a targetable vulnerability.