en
Scientific article
Open access
English

AMP-Activated Protein Kinase Contributes to Apoptosis Induced by the Bcl-2 Inhibitor Venetoclax in Acute Myeloid Leukemia

Published inCancers, vol. 13, no. 23, 5966
Publication date2021-11-27
First online date2021-11-27
Abstract

The treatment of acute myeloid leukemia (AML) remains a challenge especially among the elderly. The Bcl-2 inhibitor venetoclax recently showed significant survival benefits in AML patients when combined to low-dose cytarabine or azacitidine. Bcl-2 inhibition initiate mitochondrial apoptosis, but also respiration and cellular ATP production in AML. AMP-Activated Protein Kinase (AMPK) is a central energy sensor activated by increased AMP:ATP ratio to restore the cellular energy balance. Unexpectedly, we observed that venetoclax inhibited AMPK activity through caspase-dependent degradation of AMPK subunits in AML cells. On the other hand, genetic models of AMPK invalidation and re-expression suggested that AMPK participated to the early stages of apoptotic response through a negative regulation of multi-domain anti-apoptotic effectors such as Mcl-1 or Bcl-xL. Together our results suggested a new link between AMPK and Bcl-2-dependent mitochondrial apoptosis that participated to the anti-leukemic activity of venetoclax in AML.

eng
Keywords
  • AML
  • AMPK
  • Venetoclax
Citation (ISO format)
LEGRAND SOBOLEWSKI, Noémie et al. AMP-Activated Protein Kinase Contributes to Apoptosis Induced by the Bcl-2 Inhibitor Venetoclax in Acute Myeloid Leukemia. In: Cancers, 2021, vol. 13, n° 23, p. 5966. doi: 10.3390/cancers13235966
Main files (1)
Article (Published version)
Secondary files (1)
Identifiers
ISSN of the journal2072-6694
112views
40downloads

Technical informations

Creation03/22/2022 12:44:00 PM
First validation03/22/2022 12:44:00 PM
Update time03/16/2023 7:46:23 AM
Status update03/16/2023 7:46:21 AM
Last indexation05/06/2024 11:42:47 AM
All rights reserved by Archive ouverte UNIGE and the University of GenevaunigeBlack