Targeting the metabolism of leukemia stem cells as a novel therapeutic strategy

Abstract

Background: Acute myeloid leukemia (AML) is a cancer with a high mortality rate. AML affects blood cells in the bone marrow and has a five-year survival rate of ≈24%. Standard treatment strategies for AML include chemotherapy, radiotherapy, and hematopoietic stem cell transplantation. Due to the heterogeneous population of cancer cells and a lack of understanding of AML, therapies are often not successful. Experimental data have shown that a subpopulation of cancer cells called cancer stem cells (CSCs) possess all the characteristics of normal stem cells (self-renewal, differentiation into various cell types) and may play a part in the development of cancer. Hence, researchers are attempting to better delineate the scientific understanding of the biology of CSCs and their role in cancer development.

Therapeutic strategies: A low oxidative state as a potentially frequent property of CSC and the lack of glycolytic activity in stem cells may be inherent features of cancers. If this hypothesis is scientifically valid, then therapeutic strategies based on the assumption that tumors are reliant preferentially on glycolysis may fail the null hypothesis. Moreover, the paradoxical dependence on oxidative phosphorylation of the reactive oxygen species leukemia stem cells (ROS-low LSC)-enriched subset of CSC is part of a capacious metabolic adaptation of these cells because they successfully maintain survival despite a dramatically reduced overall metabolic rate.

Conclusions: The findings described by Lagadinou et al. in 2013 are provocative and a syllogistic biomedical step for-ward towards unravelling the understanding of CSCs and their role in the development and progression of cancer.