Mitochondrial metabolism: powering new directions in acute myeloid leukemia

Abstract

There has been an explosion of knowledge about the role of metabolism and the mitochondria in acute myeloid leukemia (AML). We have also recently seen several waves of novel therapies change the treatment landscape for AML, such as the selective B-cell lymphoma 2 (BCL-2) inhibitor venetoclax. In this new context, we review the rapidly advancing literature on the role of metabolism and the mitochondria in AML pathogenesis, and how these are interwoven with the mechanisms of action for novel therapeutics in AML. We also review the role of oxidative phosphorylation (OxPhos) in maintaining leukemia stem cells (LSCs), how recurrent genomic alterations in AML alter downstream metabolism, and focus on how the BCL-2 pathway and the mitochondria are inextricably linked in AML. Thus, we provide an overview of the mitochondria and metabolism in the context of our new therapeutic world for AML and outline how targeting these vulnerabilities may produce novel therapeutic strategies.

Keywords:

• Acute myeloid leukemia
• mitochondria
• OxPhos
• BCL-2
• venetoclax therapy resistance

Disclosure statement

The authors declare no conflict of interest.

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

F.K. was supported by grants from the BC Cancer Foundation and the Leukemia Lymphoma Society of Canada (LLSC). RJS is supported by grants from the Leukemia Lymphoma Society of Canada, the Canadian Institutes of Health Research (202002LFC-439884), and the Clinician Investigator Program Scholar Award at the University of British Columbia.