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:10.1038/s41467-022-29639-0

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

Affiliations

Ayşegül Erdem: Department of Experimental Hematology, University Medical Center Groningen, University of Groningen, Hanzeplein 1
Silvia Marin: Department of Biochemistry and Molecular Biomedicine, Faculty of Biology, University of Barcelona, Avda. Diagonal 643
Diego A. Pereira-Martins: Department of Experimental Hematology, University Medical Center Groningen, University of Groningen, Hanzeplein 1
Marjan Geugien: Department of Experimental Hematology, University Medical Center Groningen, University of Groningen, Hanzeplein 1
Alan Cunningham: Department of Experimental Hematology, University Medical Center Groningen, University of Groningen, Hanzeplein 1
Maurien G. Pruis: Department of Experimental Hematology, University Medical Center Groningen, University of Groningen, Hanzeplein 1
Isabel Weinhäuser: Department of Experimental Hematology, University Medical Center Groningen, University of Groningen, Hanzeplein 1
Albert Gerding: Department of Laboratory Medicine, University Medical Center Groningen, University of Groningen, Hanzeplein 1
Barbara M. Bakker: Laboratory of Pediatrics, Section Systems Medicine of Metabolism and Signaling, University Medical Center Groningen, University of Groningen
Albertus T. J. Wierenga: Department of Experimental Hematology, University Medical Center Groningen, University of Groningen, Hanzeplein 1
Eduardo M. Rego: Hematology Division, LIM31, Faculdade de Medicina, University of São Paulo
Gerwin Huls: Department of Experimental Hematology, University Medical Center Groningen, University of Groningen, Hanzeplein 1
Marta Cascante: Department of Biochemistry and Molecular Biomedicine, Faculty of Biology, University of Barcelona, Avda. Diagonal 643
Jan Jacob Schuringa: Department of Experimental Hematology, University Medical Center Groningen, University of Groningen, Hanzeplein 1

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.

Published in Nature Communications

ISSN: 2041-1723 (Online)
Publisher: Nature Portfolio
Country of publisher: United Kingdom
LCC subjects: Science
Website: https://www.nature.com/ncomms/

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