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Review
. 2022 Jun 8:12:846149.
doi: 10.3389/fonc.2022.846149. eCollection 2022.

Deciphering Metabolic Adaptability of Leukemic Stem Cells

Sweta B Patel  1   2 , Travis Nemkov  3 , Angelo D'Alessandro  3 , Robert S Welner  1
Affiliations
Review

Deciphering Metabolic Adaptability of Leukemic Stem Cells

Sweta B Patel et al. Front Oncol. .

Abstract

Therapeutic targeting of leukemic stem cells is widely studied to control leukemia. An emerging approach gaining popularity is altering metabolism as a potential therapeutic opportunity. Studies have been carried out on hematopoietic and leukemic stem cells to identify vulnerable pathways without impacting the non-transformed, healthy counterparts. While many metabolic studies have been conducted using stem cells, most have been carried out in vitro or on a larger population of progenitor cells due to challenges imposed by the low frequency of stem cells found in vivo. This creates artifacts in the studies carried out, making it difficult to interpret and correlate the findings to stem cells directly. This review discusses the metabolic difference seen between hematopoietic stem cells and leukemic stem cells across different leukemic models. Moreover, we also shed light on the advancements of metabolic techniques and current limitations and areas for additional research of the field to study stem cell metabolism.

Keywords: hematopoietic stem cells; leukemia; leukemic stem cells (LSCs); metabolic techniques; metabolism.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Metabolic regulation of HSCs. Young hematopoitic stem cells have a higher mitochondrial mass, but the mitochondria are inactive, and the cells rely on glycolysis. However, under stress, increase in metabolic activity, OXPHOS (oxidative phosphorylation) and FAO (fatty acid oxidation) lead to impaired stem cell function. This phenomenon can be reversed by increasing mitochondrial membrane potential (MMP).
Figure 2
Figure 2
Metabolic difference between AML and CML LSCs. AML LSCs are reliant on OxPhos and yet have low ROS level controlled by mitophagy. Moreover, AML LSCs use amino acid and fatty acid metabolism to fuel the citric acid cycle. CML LSCs on the other hand exhibit increased mitochondrial biogenesis, FAO, OXPHOS and ROS. ROS leads to DNA instability and subsequently. Causes mutation in the BCR-ABL oncogene, rendering the cells resistant to drug treatment.
Figure 3
Figure 3
Metabolic difference between ALL and CLL LSCs. B-ALL LSCs are reliant on Pentose phosphate pathway (PPP) and glycolysis where as T-ALL LSCs rely more on glutamine metabolism. CLL on the other had sees an increase in ROS and is reliant on OXPHOS. Increase in glutathione metabolism is also reported as an antioxidant to the high amount of ROS.
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