Extinguishing the Embers: Targeting AML Metabolism

Trends Mol Med. 2021 Apr;27(4):332-344. doi: 10.1016/j.molmed.2020.10.001. Epub 2020 Oct 26.

Abstract

Acute myeloid leukemia (AML) is a cancer derived from the myeloid lineage of blood cells, characterized by overproduction of leukemic blasts. Although therapeutic improvements have made a significant impact on the outcomes of patients with AML, survival rates remain low due to a high incidence of relapse. Similar to how wildfires can reignite from hidden embers not extinguished from an initial round of firefighting, leukemic stem cells (LSCs) are the embers remaining after completion of traditional chemotherapeutic treatments. LSCs exhibit a unique metabolic profile and contain metabolically distinct subpopulations. In this review, we detail the metabolic features of LSCs and how thetse characteristics promote resistance to traditional chemotherapy. We also discuss new therapeutic approaches that target metabolic vulnerabilities of LSC to selectively eradicate them.

Keywords: AML; LSC; acute myeloid leukemia; leukemic stem cells; mitochondrial metabolism; oxidative phosphorylation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antineoplastic Agents / therapeutic use
  • Drug Resistance, Neoplasm
  • Drug Therapy
  • Humans
  • Leukemia, Myeloid, Acute* / drug therapy
  • Leukemia, Myeloid, Acute* / metabolism
  • Mitochondria / metabolism
  • Neoplastic Stem Cells* / drug effects
  • Neoplastic Stem Cells* / metabolism
  • Oxidative Phosphorylation / drug effects*
  • Reactive Oxygen Species / metabolism

Substances

  • Antineoplastic Agents
  • Reactive Oxygen Species