The DOI matches its Crossref record; 59 of the 59 references it cites were found in a registry or an index.
Adaptive response to inflammation contributes to sustained myelopoiesis and confers a competitive advantage in myelodysplastic syndrome HSCs
Open accessAbstract
Despite evidence of chronic inflammation in myelodysplastic syndrome (MDS) and cell-intrinsic dysregulation of Toll-like receptor (TLR) signaling in MDS hematopoietic stem and progenitor cells (HSPCs), the mechanisms responsible for the competitive advantage of MDS HSPCs in an inflammatory milieu over normal HSPCs remain poorly defined. Here, we found that chronic inflammation was a determinant for the competitive advantage of MDS HSPCs and for disease progression. The cell-intrinsic response of MDS HSPCs, which involves signaling through the noncanonical NF-κB pathway, protected these cells from chronic inflammation as compared to normal HSPCs. In response to inflammation, MDS HSPCs switched from canonical to noncanonical NF-κB signaling, a process that was dependent on TLR-TRAF6-mediated activation of A20. The competitive advantage of TLR-TRAF6-primed HSPCs could be restored by deletion of A20 or inhibition of the noncanonical NF-κB pathway. These findings uncover the mechanistic basis for the clonal dominance of MDS HSPCs and indicate that interfering with noncanonical NF-κB signaling could prevent MDS progression.
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“and exhibit a toll-like receptor–TNF receptor associated factor 6A (TLR-TRAF6A) and noncanonical NF-κB–dependent competitive advantage during low-grade inflammation.17”
From Aging drives Tet2 +/− clonal hematopoiesis via IL-1 signaling (2023) · cites this paper as [17]
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The non-canonical NF-κB pathway in immunity and inflammation
Sun, S. (2017) · Nature reviews. Immunology · doi:10.1038/nri.2017.52 · Cited by 1,959
De-ubiquitination and ubiquitin ligase domains of A20 downregulate NF-κB signalling
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Self-citationHaeussler, M., Schönig, K., Eckert, H., Eschstruth, A., Mianné, J., Renaud, J.-B., Schneider-Maunoury, S., Shkumatava, A., Teboul, L., Kent, J., et al. (2016) · Genome biology · doi:10.1186/s13059-016-1012-2 · Cited by 1,756
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Self-citationFailure to Regulate TNF-Induced NF-κB and Cell Death Responses in A20-Deficient Mice
Lee, E. G., Boone, D. L., Chai, S., Libby, S. L., Chien, M., Lodolce, J. P., & Ma, A. (2000) · Science · doi:10.1126/science.289.5488.2350 · Cited by 1,409
Self-citationTet2 is required to resolve inflammation by recruiting Hdac2 to specifically repress IL-6
Zhang, Q., Zhao, K., Shen, Q., Han, Y., Gu, Y., Li, X., Zhao, D., Liu, Y., Wang, C., Zhang, X., et al. (2015) · Nature · doi:10.1038/nature15252 · Cited by 807
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Identification of miR-145 and miR-146a as mediators of the 5q– syndrome phenotype
Starczynowski, D. T., Kuchenbauer, F., Argiropoulos, B., Sung, S., Morin, R., Muranyi, A., Hirst, M., Hogge, D., Marra, M., Wells, R. A., et al. (2010) · Nature Medicine · doi:10.1038/nm.2054 · Cited by 577
Self-citationInflammation: a key regulator of hematopoietic stem cell fate in health and disease
Pietras, E. M. (2017) · Blood · doi:10.1182/blood-2017-06-780882 · Cited by 417
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Self-citationAging drives Tet2 +/− clonal hematopoiesis via IL-1 signaling
Caiado, F., Kovtonyuk, L. V., Gonullu, N. G., Fullin, J., Boettcher, S., & Manz, M. G. (2023) · Blood · doi:10.1182/blood.2022016835 · Cited by 161
Metadata
- Authors
- Muto, T., Walker, C. S., Choi, K., Hueneman, K., Smith, M. A., Gul, Z., Garcia-Manero, G., Ma, A., Zheng, Y., & Starczynowski, D. T.
- Affiliations
- Cincinnati Children's Hospital Medical Center (US)
- University of Cincinnati (US)
- University of California, San Francisco (US)
- Corresponding author
- Starczynowski, Daniel T.
- ORCID
- Venue
- Nature Immunology
- Published
- 2020-04-20
- Volume
- 21
- Issue
- 5
- Pages
- 535-545
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- PMC
- PMC7402480
- OpenAlex
- W3017327186
- Cited by
- 155
- References
- 59
- Citations by year
- 2026: 11 · 2025: 21 · 2024: 30 · 2023: 24 · 2022: 24 · 2021: 28 · 2020: 16
- FWCI
- 14.53
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature Immunology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R35HL135787)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK102759, R01DK113639)
- Topics
- Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Keywords
- myelodysplastic syndrome, hematopoietic stem and progenitor cells, chronic inflammation, non-canonical NF-κB signaling, Toll-like receptor signaling, TRAF6, A20, clonal dominance, myelopoiesis, disease progression, competitive advantage
- MeSH terms
- Tumor Necrosis Factor alpha-Induced Protein 3, Aged, Animals, Cell Differentiation, Cells, Cultured, Hematopoietic Stem Cells, Humans, Inflammation, Male, Mice, Transgenic, Myelodysplastic Syndromes, Signal Transduction, NF-kappa B, Myelopoiesis, TNF Receptor-Associated Factor 6, Toll-Like Receptors, Mice
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