Targeting Mitochondrial Oxidative Phosphorylation Eradicates Acute Myeloid Leukemic Stem Cells

Meixi Peng; Yongxiu Huang; Ling Zhang; Xueya Zhao; Yu Hou

doi:10.3389/fonc.2022.899502

Targeting Mitochondrial Oxidative Phosphorylation Eradicates Acute Myeloid Leukemic Stem Cells

Front Oncol. 2022 Apr 29:12:899502. doi: 10.3389/fonc.2022.899502. eCollection 2022.

Authors

Meixi Peng¹, Yongxiu Huang^{2

3}, Ling Zhang⁴, Xueya Zhao¹, Yu Hou¹

Affiliations

¹ Biology Science Institutes, Chongqing Medical University, Chongqing, China.
² Clinical Hematology, Third Military Medical University (Army Medical University), Chongqing, China.
³ School of Medicine, Chongqing University, Chongqing, China.
⁴ Key Laboratory of Laboratory Medical Diagnostics Designated by the Ministry of Education, School of Laboratory Medicine, Chongqing Medical University, Chongqing, China.

Abstract

Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy characterized by multiple cytogenetic and molecular abnormalities, with a very poor prognosis. Current treatments for AML often fail to eliminate leukemic stem cells (LSCs), which perpetuate the disease. LSCs exhibit a unique metabolic profile, especially dependent on oxidative phosphorylation (OXPHOS) for energy production. Whereas, normal hematopoietic stem cells (HSCs) and leukemic blasts rely on glycolysis for adenosine triphosphate (ATP) production. Thus, understanding the regulation of OXPHOS in LSCs may offer effective targets for developing clinical therapies in AML. This review summarizes these studies with a focus on the regulation of the electron transport chain (ETC) and tricarboxylic acid (TCA) cycle in OXPHOS and discusses potential therapies for eliminating LSCs.

Keywords: electron transport chain; leukemic stem cells (LSCs); mitochondria; oxidative phosphorylation (OXPHOS); tricarboxylic acid cycle (TCA cycle).

Publication types

Systematic Review