ArticleJournal of immunology (Baltimore, Md. : 1950)2015
Modulation of the IL-6 Receptor α Underlies GLI2-Mediated Regulation of Ig Secretion in Waldenström Macroglobulinemia Cells.
Article in Journal of immunology (Baltimore, Md. : 1950), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 22 citations in OpenAlex.
- Decoding Waldenström Macroglobulinemia Through Genomics, Epigenomics and Cellular Interactions.International journal of molecular sciences · 2026Review
- GLI3 Is Required for M2 Macrophage Polarization and M2-Mediated Waldenström Macroglobulinemia Growth and Survival.International journal of molecular sciences · 2024Article
- Nucleic Acid Biomarkers in Waldenström Macroglobulinemia and IgM-MGUS: Current Insights and Clinical Relevance.Diagnostics (Basel, Switzerland) · 2022Review
- A novel mechanism of regulation of the oncogenic transcription factor GLI3 by toll-like receptor signaling.Oncotarget · 2022Article
- Macrophage Polarization States in the Tumor Microenvironment.International journal of molecular sciences · 2021Review
- Epigenetic targeting of Waldenström macroglobulinemia cells with BET inhibitors synergizes with BCL2 or histone deacetylase inhibition.Epigenomics · 2021Article
- GLI3: a mediator of genetic diseases, development and cancer.Cell communication and signaling : CCS · 2020Review
- Human MYD88L265P is insufficient by itself to drive neoplastic transformation in mature mouse B cells.Blood advances · 2019Article
- Targeting IL-6 receptor reduces IgM levels and tumor growth in Waldenström macroglobulinemia.Oncotarget · 2019Article
- Bone marrow stromal cells interaction with titanium; Effects of composition and surface modification.PloS one · 2019Article
- Use of Laplacian Heat Diffusion Algorithm to Infer Novel Genes With Functions Related to Uveitis.Frontiers in genetics · 2018Article
- Novel Molecular Mechanism of Regulation of CD40 Ligand by the Transcription Factor GLI2.Journal of immunology (Baltimore, Md. : 1950) · 2017Article
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Ig secretion by terminally differentiated B cells is an important component of the immune response to foreign pathogens. Its overproduction is a defining characteristic of several B cell malignancies, including Waldenström macroglobulinemia (WM), where elevated IgM is associated with significant morbidity and poor prognosis. Therefore, the identification and characterization of the mechanisms controlling Ig secretion are of great importance for the development of future therapeutic approaches for this disease. In this study, we define a novel pathway involving the oncogenic transcription factor GLI2 modulating IgM secretion by WM malignant cells. Pharmacological and genetic inhibition of GLI2 in WM malignant cells resulted in a reduction in IgM secretion. Screening for a mechanism identified the IL-6Rα (gp80) subunit as a downstream target of GLI2 mediating the regulation of IgM secretion. Using a combination of expression, luciferase, and chromatin immunoprecipitation assays we demonstrate that GLI2 binds to the IL-6Rα promoter and regulates its activity as well as the expression of this receptor. Additionally, we were able to rescue the reduction in IgM secretion in the GLI2 knockdown group by overexpressing IL-6Rα, thus defining the functional significance of this receptor in GLI2-mediated regulation of IgM secretion. Interestingly, this occurred independent of Hedgehog signaling, a known regulator of GLI2, as manipulation of Hedgehog had no effect on IgM secretion. Given the poor prognosis associated with elevated IgM in WM patients, components of this new signaling axis could be important therapeutic targets.
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