Page 67 - JCTR-11-5

Journal of Clinical and
Translational Research Metabolism of healthy and leukemic stem cells

and LSC survival but also highlight specific bioenergetic Visualization: Gavin M. Traber, Emely A. Pacheco, Edziu
vulnerabilities within LSCs that may serve as therapeutic Franczak, Ansh Kumar
targets. By gaining a deeper understanding of the metabolic Writing–original draft: Gavin M. Traber, Emely A. Pacheco,
characteristics that distinguish healthy HSC activity Edziu Franczak, Ansh Kumar
from dysregulated LSC activity, researchers can better Writing–review & editing: Gavin M. Traber, Emely A.
understand the mechanisms that sustain healthy function Pacheco, Edziu Franczak, Kelsey H. Fisher-Wellman,
and identify those that lead to oncogenic transformation Kathleen M. Sakamoto
and other hematological disorders.
Collectively, these findings suggest that while LSCs are Ethics approval and consent to participate
metabolically altered for survival, these unique adaptations Not applicable.
may serve as targets for therapeutic intervention. Strategies
that impair mitochondrial metabolism disrupt FAO or target Consent for publication
nutrient-sensing pathways may offer promising approaches Not applicable.
for selectively eliminating LSCs without compromising
healthy hematopoiesis. As our understanding of stem Availability of data
cell metabolism deepens, these insights will guide the Not applicable.
development of next-generation therapies to improve
treatment durability and prevent relapse in hematologic References
malignancies such as AML and CML.
1. Olson OC, Kang YA, Passegue E. Normal hematopoiesis is a
Acknowledgments balancing act of self-renewal and regeneration. Cold Spring
Harb Perspect Med. 2020;10(12):a035519.
None.
doi: 10.1101/cshperspect.a035519
Funding 2. Morrison SJ, Scadden DT. The bone marrow niche for
haematopoietic stem cells. Nature. 2014;505(7483):327-334.
Gavin M. Traber is supported by the National Institute
of Diabetes and Digestive and Kidney Diseases (NIDDK; doi: 10.1038/nature12984
TL1DK139565). Kathleen M. Sakamoto is funded by 3. Barreto IV, Pessoa F, Machado CB, et al. Leukemic stem
NIDDK (DK136961), the Leukemia and Lymphoma cell: A mini-review on clinical perspectives. Front Oncol.
Society (R6518-23), the Pediatric Cancer Research 2022;12:931050.
Foundation (grant number: 858010), the Stanford doi: 10.3389/fonc.2022.931050
Innovation Medicine Accelerator, Cure Childhood Cancer
(grant number: 641095), and the Department of Defense 4. Seita J, Weissman IL. Hematopoietic stem cell: Self-renewal
(RA220017). Emely A. Pacheco and Kelsey H. Fisher- versus differentiation. Wiley Interdiscip Rev Syst Biol Med.
2010;2(6):640-653.
Wellman are supported by the National Cancer Institute
(P01CA171983 and R01CA299332). Emely A. Pacheco, doi: 10.1002/wsbm.86
Edziu Franczak, and Kelsey H. Fisher-Wellman are 5. Morganti C, Cabezas-Wallscheid N, Ito K. Metabolic
supported by the National Cancer Institute (P01CA171983 regulation of hematopoietic stem cells. Hemasphere.
and R01CA299332). 2022;6(7):e740.
Conflict of interest doi: 10.1097/HS9.0000000000000740
6. Mann Z, Sengar M, Verma YK, Rajalingam R, Raghav PK.
Kathleen M. Sakamoto is an Editorial Board Member of Hematopoietic stem cell factors: Their functional role
this journal, but was not in any way involved in the editorial in self-renewal and clinical aspects. Front Cell Dev Biol.
and peer-review process conducted for this paper, directly 2022;10:664261.
or indirectly. Separately, other authors declared that they doi: 10.3389/fcell.2022.664261
have no known competing financial interests or personal
relationships that could have influenced the work reported 7. Zhang CC, Lodish HF. Cytokines regulating hematopoietic
in this paper. stem cell function. Curr Opin Hematol. 2008;15(4):307-311.
doi: 10.1097/MOH.0b013e3283007db5
Author contributions
8. Simsek T, Kocabas F, Zheng J, et al. The distinct metabolic
Conceptualization: Gavin M. Traber, Emely A. Pacheco, profile of hematopoietic stem cells reflects their location in a
Kelsey H. Fisher-Wellman, Kathleen M. Sakamoto hypoxic niche. Cell Stem Cell. 2010;7(3):380-390.

Volume 11 Issue 5 (2025) 61 doi: 10.36922/JCTR025320053