Page 56 - JCTR-11-5

Journal of Clinical and

Translational Research

REVIEW ARTICLE
Metabolomics of healthy hematopoietic stem

cells and leukemia stem cells

Gavin M. Traber 1 , Emely A. Pacheco 2 , Ansh Kumar 1 , Edziu Franczak 2 ,
Kelsey H. Fisher-Wellman 2 , and Kathleen M. Sakamoto *
1
1 Department of Pediatrics, Stanford University School of Medicine, Stanford University, Stanford,
California, United States of America
2 Department of Cancer Biology, Wake Forest University School of Medicine, Wake Forest University,
Winston-Salem, North Carolina, United States of America

Abstract

Background: Hematopoietic stem cells (HSCs) reside in the bone marrow (BM)
and sustain life-long hematopoiesis by balancing quiescence, self-renewal, and
differentiation. A key feature distinguishing quiescent HSCs from their activated
counterparts is a shift in their metabolic profile, including changes in glycolytic
flux and mitochondrial oxidative metabolism. Disruption of HSC homeostasis
can lead to hematologic diseases such as BM failure, clonal hematopoiesis,
or oncogenic transformation into leukemia stem cells (LSCs). Similar to HSCs,
*Corresponding author: LSCs retain stem-like characteristics but acquire malignant features, including
Kathleen Sakamoto drug resistance and a reprogrammed metabolism, which results in distinct
(kmsakamo@stanford.edu) metabolic profiles that contribute to their pathogenesis. Aim: This review
Citation: Traber GM, Pacheco EA, summarizes the key metabolic characteristics distinguishing healthy quiescent
Kumar A, et al. Metabolomics of and active HSCs from oncogenic LSCs. In addition, we highlight modern tools
healthy hematopoietic stem cells
and leukemia stem cells. J Clin for investigating the metabolome, which enable the identification of novel
Transl Res. 2025;11(5):50-68. metabolites, metabolic interactions, pathways, and potential targets for diagnosis
doi: 10.36922/JCTR025320053 or therapeutic intervention in hematologic diseases. Conclusion: Metabolic
Received: August 8, 2025 regulation is essential for maintaining HSC quiescence, self-renewal, and lineage
commitment, whereas its disruption often underlies oncogenic transformation
Revised: September 6, 2025
into LSCs. Advances in metabolic profiling reveal key differences between
Accepted: September 9, 2025 healthy HSCs and LSCs and identify LSC vulnerabilities that sustain survival
Published online: October 8, 2025 and therapeutic resistance. Targeting these hijacked metabolic pathways may
facilitate the development of LSC-specific treatment while preserving normal
Copyright: © 2025 Author(s).
This is an open-access article hematopoiesis. Further investigation of stem cell metabolism will be critical for
distributed under the terms of the translating these insights into effective treatments for hematologic malignancies.
Creative Commons AttributionNon- Relevance for patients: Understanding the metabolic profiles of healthy HSCs
Commercial 4.0 International (CC
BY-NC 4.0), which permits all and LSCs can facilitate the development of innovative techniques, technologies,
non-commercial use, distribution, and therapeutics. These advances can be applied to the identification, treatment,
and reproduction in any medium, and prevention of hematologic disease. By elucidating the metabolome of LSCs,
provided the original work is
properly cited. therapies can be designed to selectively target their unique metabolic pathways,
dependencies, and resistance mechanisms.
Publisher’s Note: AccScience
Publishing remains neutral with
regard to jurisdictional claims in
published maps and institutional Keywords: Hematopoietic stem cells; Leukemia stem cells; Metabolism; Metabolomics
affiliations.

Volume 11 Issue 5 (2025) 50 doi: 10.36922/JCTR025320053