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Modulation of cell proliferation and cytokine production in acute myeloblastic leukemia by interleukin-1 receptor antagonist and lack of its expression by leukemic cells
Open accessAbstract
Interleukin-1 (IL-1) is spontaneously produced by acute myeloblastic leukemia (AML) cells. IL-1 also induces synthesis of colony-stimulating factors (CSFs) and sustains leukemic growth. An IL-1-specific inhibitor has been recently purified and cloned; this molecule binds to IL-1 receptors but has no IL-1 activity, fulfilling the characteristics of an IL-1 receptor antagonist (IL-1ra). Because high-affinity binding sites for IL-1ra were shown on AML cells by radioligand binding studies, we studied the effect of IL-1ra on the proliferative activity of blast cells isolated from 16 cases of AML. In each case, spontaneous proliferation was inhibited by addition of the IL-1ra in a dose- dependent manner (1 to 100 ng/mL). Culture supernatants of unstimulated leukemic cells contained IL-1 beta and granulocyte-macrophage CSF (GM- CSF), but when incubated with the IL-1ra, a reduction or disappearance of GM-CSF was observed in 8 of 10 cases, whereas spontaneous IL-1 production was reduced in four of seven cases. By Northern hybridization, IL-1 beta gene transcripts were shown in 20 of 23 AML cases, whereas IL-1ra-specific messenger RNA was present in only two of the patients studied. These data show a role for IL-1 in the spontaneous proliferation and cytokine production of AML cells and suggest that an imbalanced synthesis of IL-1 and of its natural receptor antagonist may contribute to the unrestricted growth of AML cells.
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“In particular, the SASP-associated cytokines TNF, IFN, and IL-6 all play significant roles in the pathogenesis of myeloproliferative neoplasms (MPNs), 52 MDSs, 53 and acute myeloid leukemia (AML).54”
From Inflammatory bone marrow microenvironment (2019) · cites this paper as [54]
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Metadata
- Authors
- Rambaldi, A., Torcia, M., Bettoni, S., Vannier, E., Barbui, T., Shaw, A., Dinarello, C., & Cozzolino, F.
- Affiliations
- Merck & Co., Inc., Rahway, NJ, USA (United States) (US)
- Division of Hematology, Ospedali Riuniti, Bergamo, Italy.
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 1991-12-15
- Volume
- 78
- Issue
- 12
- Pages
- 3248-3253
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W2395259494
- Cited by
- 129
- References
- 29
- Citations by year
- 2025: 2 · 2024: 1 · 2023: 2 · 2022: 2 · 2021: 1 · 2019: 2 · 2018: 1 · 2017: 1 · 2016: 2 · 2015: 2 · 2014: 1 · 2013: 3 · 2012: 3
- FWCI
- 9.89
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Blood (publishedVersion)
- PubMed (publishedVersion)
- Florence Research (University of Florence) (submittedVersion, other-oa)
- Funders
- National Institutes of Health (15614, AI‐15614)
- National Institute of Allergy and Infectious Diseases (AI‑15614)
- Topics
- Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
- Life Sciences › Immunology and Microbiology › Immunology › Cytokine Signaling Pathways and Interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinoids in leukemia and cellular processes
- Keywords
- acute myeloid leukemia, interleukin-1 receptor antagonist, IL-1β, cell proliferation, cytokine production, GM-CSF, leukemia cell proliferation
- MeSH terms
- Binding, Competitive, Cell Division, Humans, Interleukin-1, Kinetics, Proteins, Receptors, Immunologic, Recombinant Proteins, RNA, Messenger, Sialoglycoproteins, Tumor Cells, Cultured, Blotting, Northern, Leukemia, Myeloid, Acute, Gene Expression, Granulocyte-Macrophage Colony-Stimulating Factor, Cytokines, Receptors, Interleukin-1, Interleukin 1 Receptor Antagonist Protein
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