The DOI matches its Crossref record; 63 of the 63 references it cites were found in a registry or an index.
Induction of myelodysplasia by myeloid-derived suppressor cells
Open accessAbstract
Myelodysplastic syndromes (MDS) are age-dependent stem cell malignancies that share biological features of activated adaptive immune response and ineffective hematopoiesis. Here we report that myeloid-derived suppressor cells (MDSC), which are classically linked to immunosuppression, inflammation, and cancer, were markedly expanded in the bone marrow of MDS patients and played a pathogenetic role in the development of ineffective hematopoiesis. These clonally distinct MDSC overproduce hematopoietic suppressive cytokines and function as potent apoptotic effectors targeting autologous hematopoietic progenitors. Using multiple transfected cell models, we found that MDSC expansion is driven by the interaction of the proinflammatory molecule S100A9 with CD33. These 2 proteins formed a functional ligand/receptor pair that recruited components to CD33’s immunoreceptor tyrosine-based inhibition motif (ITIM), inducing secretion of the suppressive cytokines IL-10 and TGF-β by immature myeloid cells. S100A9 transgenic mice displayed bone marrow accumulation of MDSC accompanied by development of progressive multilineage cytopenias and cytological dysplasia. Importantly, early forced maturation of MDSC by either all-trans-retinoic acid treatment or active immunoreceptor tyrosine-based activation motif–bearing (ITAM-bearing) adapter protein (DAP12) interruption of CD33 signaling rescued the hematologic phenotype. These findings indicate that primary bone marrow expansion of MDSC driven by the S100A9/CD33 pathway perturbs hematopoiesis and contributes to the development of MDS.
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“MDSCs are sufficient to create an MDS phenotype in murine experiments, and targeting them or their expansion leads to reconstitution of normal hematopoiesis.76,77”
From Inflammatory bone marrow microenvironment (2019) · cites this paper as [76]
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Myeloid-derived-suppressor cells as regulators of the immune system
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Metadata
- Authors
- Chen, X., Eksioglu, E. A., Zhou, J., Zhang, L., Djeu, J., Fortenbery, N., Epling-Burnette, P., Van Bijnen, S., Dolstra, H., Cannon, J., Youn, J.-I., Donatelli, S. S., Qin, D., De Witte, T., Tao, J., Wang, H., Cheng, P., Gabrilovich, D. I., List, A., & Wei, S.
- Affiliations
- Moffitt Cancer Center (US)
- Radboud University Medical Center (NL)
- University of South Florida (US)
- Corresponding author
- Wei, Sheng
- ORCID
- Venue
- Journal of Clinical Investigation
- Published
- 2013-10-15
- Volume
- 123
- Issue
- 11
- Pages
- 4595-4611
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC3809779
- OpenAlex
- W2111063688
- Cited by
- 316
- References
- 63
- Citations by year
- 2026: 17 · 2025: 18 · 2024: 19 · 2023: 28 · 2022: 31 · 2021: 43 · 2020: 30 · 2019: 26 · 2018: 23 · 2017: 25 · 2016: 30 · 2015: 17 · 2014: 9
- FWCI
- 10.33
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Radboud Repository (Radboud University) (submittedVersion, other-oa)
- Radboud Repository (Radboud University) (submittedVersion)
- Funders
- National Institutes of Health (AI056213)
- National Cancer Institute (T32CA115308, R01CA131076, R01CA100062, P30CA076292)
- National Institute of Allergy and Infectious Diseases (AI056213, R01AI056213)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Keywords
- myelodysplastic syndrome, myeloid-derived suppressor cells, ineffective hematopoiesis, S100A9, CD33, immunoreceptor tyrosine-based inhibition motif, ITAM, DAP12, IL-10, TGF-beta, bone marrow, all-trans retinoic acid, transgenic mice
- MeSH terms
- Animals, Disease Models, Animal, Female, Hematopoiesis, HLA-DR Antigens, Humans, Ligands, Male, Mice, Transgenic, Myelodysplastic Syndromes, Signal Transduction, Mice, Knockout, Adoptive Transfer, Myeloid Cells, Calgranulin A, Calgranulin B, Mice, Cellular Microenvironment, Sialic Acid Binding Ig-like Lectin 3
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