ArticleHaematologica2020
Oncogenic D816V-KIT signaling in mast cells causes persistent IL-6 production.
Article in Haematologica, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 37 citations in OpenAlex.
- Mast Cells in the Developing Brain.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Review
- Enhanced PIEZO1 expression in mast cells of mastocytosis skin lesions: Relevance to Darier's sign.Journal of the European Academy of Dermatology and Venereology : JEADV · 2026Article
- Prolonged IL-33 Exposure Switches the Secreted Mast Cell Cytokine Profile From Pro-Inflammatory to Pro-Tolerant.Allergy · 2026Article
- Gut-Brain Inflammation and Disrupted Homeostasis Due to Activation of Mast Cells and Microglia.International journal of molecular sciences · 2026Review
- Review
- Drug Metabolism and Pharmacokinetics of Oxazolo[4,5-Pharmaceutics · 2025Article
- Inhibition of colorectal carcinogenesis by sunitinib malate: disruption of the IL-6/STAT3/c-MYC/TWIST/MMP2 autocrine signaling axis.Discover oncology · 2025Article
- Role of sclerostin in mastocytosis bone disease.Scientific reports · 2025Article
- Fedratinib and gandotinib induce apoptosis and enhance the efficacy of tyrosine kinase inhibitors in human mast cells.American journal of cancer research · 2025Article
- Diffuse Cutaneous Mastocytosis: A Current Understanding of a Rare Disease.International journal of molecular sciences · 2024Review
- Potential Role of Moesin in Regulating Mast Cell Secretion.International journal of molecular sciences · 2023Review
- Establishing a novel and sensitive assay for bioactivity determination of anti-CD25 antibodies.Heliyon · 2023Article
- The Role of Mast Cells in the Induction and Maintenance of Inflammation in Selected Skin Diseases.International journal of molecular sciences · 2023Review
- KIT D816V Mast Cells Derived from Induced Pluripotent Stem Cells Recapitulate Systemic Mastocytosis Transcriptional Profile.International journal of molecular sciences · 2023Article
- CRISPR/Cas9-engineering of HMC-1.2 cells renders a human mast cell line with a single D816V-KIT mutation: An improved preclinical model for research on mastocytosis.Frontiers in immunology · 2023Article
- Altered innate immune profile in blood of systemic mastocytosis patients.Clinical and translational allergy · 2022Article
- TET2 regulates immune tolerance in chronically activated mast cells.JCI insight · 2022Article
- Anaphylaxis: Focus on Transcription Factor Activity.International journal of molecular sciences · 2021Review
- Molecular Background, Clinical Features and Management of Pediatric Mastocytosis: Status 2021.International journal of molecular sciences · 2021Review
- Clinical Impact of Inherited and Acquired Genetic Variants in Mastocytosis.International journal of molecular sciences · 2021Review
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10 authors at 2 institutions in 1 country.
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Abstract
Persistent dysregulation of IL-6 production and signaling have been implicated in the pathology of various cancers. In systemic mastocytosis, increased serum levels of IL-6 associate with disease severity and progression, although the mechanisms involved are not well understood. Since systemic mastocytosis often associates with the presence in hematopoietic cells of a somatic gain-of-function variant in KIT, D816V-KIT, we examined its potential role in IL-6 upregulation. Bone marrow mononuclear cultures from patients with greater D816V allelic burden released increased amounts of IL-6 which correlated with the percentage of mast cells in the cultures. Intracellular IL-6 staining by flow cytometry and immunofluorescence was primarily associated with mast cells and suggested a higher percentage of IL-6 positive mast cells in patients with higher D816V allelic burden. Furthermore, mast cell lines expressing D816V-KIT, but not those expressing normal KIT or other KIT variants, produced constitutively high IL-6 amounts at the message and protein levels. We further demonstrate that aberrant KIT activity and signaling are critical for the induction of IL-6 and involve STAT5 and PI3K pathways but not STAT3 or STAT4. Activation of STAT5A and STAT5B downstream of D816V-KIT was mediated by JAK2 but also by MEK/ERK1/2, which not only promoted STAT5 phosphorylation but also its long-term transcription. Our study thus supports a role for mast cells and D816V-KIT activity in IL-6 dysregulation in mastocytosis and provides insights into the intracellular mechanisms. The findings contribute to a better understanding of the physiopathology of mastocytosis and suggest the importance of therapeutic targeting of these pathways.
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