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Cited by 78Acute Myeloid Leukemia ResearchHematopoietic Stem Cell TransplantationChronic Myeloid Leukemia Treatments

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Characterization and targeting of malignant stem cells in patients with advanced myelodysplastic syndromes

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Stevens, Brett M., Khan, Nabilah, D’Alessandro, Angelo, Nemkov, Travis, Winters, Amanda, Jones, Courtney L., Zhang, Wei, Pollyea, Daniel A., Jordan, Craig T.·2018·Nature Communications
DOI 10.1038/s41467-018-05984-xPMC PMC6135858
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Abstract

Myelodysplastic syndrome (MDS) is a chronic hematologic disorder that frequently evolves to more aggressive stages and in some cases leads to acute myeloid leukemia (AML). MDS arises from mutations in hematopoietic stem cells (HSCs). Thus, to define optimal therapies, it is essential to understand molecular events driving HSC pathogenesis. In this study, we report that during evolution of MDS, malignant HSCs activate distinct cellular programs that render such cells susceptible to therapeutic intervention. Specifically, metabolic analyses of the MDS stem cell compartment show a profound activation of protein synthesis machinery and increased oxidative phosphorylation. Pharmacological targeting of protein synthesis and oxidative phosphorylation demonstrated potent and selective eradication of MDS stem cells in primary human patient specimens. Taken together, our findings indicate that MDS stem cells are reliant on specific metabolic events and that such properties can be targeted prior to the onset of clinically significant AML, during antecedent MDS.

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  • Oma is a U.S. Food and Drug Administration-approved therapy for chronic myelogenous leukemia and can directly ablate MDS stem cells with aberrant levels of protein synthesis.

    “Notably, Oma is a U.S. Food and Drug Administration–approved therapy for chronic myelogenous leukemia and can directly ablate MDS stem cells with aberrant levels of protein synthesis (Stevens et al., 2018).”

    From PU.1 enforces quiescence and limits hematopoietic stem cell expansion during inflammatory stress (2021) · cites this paper as Stevens et al., 2018

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Metadata

Authors
Stevens, B. M., Khan, N., D’Alessandro, A., Nemkov, T., Winters, A., Jones, C. L., Zhang, W., Pollyea, D. A., & Jordan, C. T.
Affiliations
  • University of Colorado Anschutz (US)
  • University of Colorado Denver (US)
Corresponding author
Jordan, Craig T.
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2018-09-12
Volume
9
Issue
1
Pages
3694-3694
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-018-05984-x
PMC
PMC6135858
OpenAlex
W2890562248
Cited by
78
References
7
Citations by year
2026: 7 · 2025: 2 · 2024: 5 · 2023: 10 · 2022: 11 · 2021: 22 · 2020: 13 · 2019: 8
FWCI
7.71
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
  • University of Rochester
  • Edward P. Evans Foundation
Topics
  • Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
  • Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
  • Health Sciences › Medicine › Hematology › Chronic Myeloid Leukemia Treatments
Keywords
myelodysplastic syndrome, hematopoietic stem cells, acute myeloid leukemia, metabolic reprogramming, protein synthesis, oxidative phosphorylation, metabolic targeting, disease progression
MeSH terms
Cell Transformation, Neoplastic, Cells, Cultured, Flow Cytometry, Hematopoietic Stem Cells, Humans, Myelodysplastic Syndromes, Oxidative Phosphorylation, Leukemia, Myeloid, Acute, Interleukin-3 Receptor alpha Subunit

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