ArticleLeukemia2017
IL-10 production by CLL cells is enhanced in the anergic IGHV mutated subset and associates with reduced DNA methylation of the IL10 locus.
Article in Leukemia, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
25 citing papers in PubMed, 34 citations in OpenAlex.
- The Chronic Lymphocytic Leukemia Epigenome: A Powerful and Stable Framework for Understanding Biological and Clinical Heterogeneity.Hematology/oncology clinics of North America · 2025Review
- Effect of statins on IL-10 signaling and production by chronic lymphocytic leukemia cells.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- The Role of Tumor Microenvironment and Targeted Therapy in Chronic Lymphocytic Leukemia.Current issues in molecular biology · 2025Review
- New Derivatives of 1-(3-Methyl-1-Benzofuran-2-yl)Ethan-1-one: Synthesis and Preliminary Studies of Biological Activity.International journal of molecular sciences · 2024Article
- Analysis of Mutational Status ofInternational journal of molecular sciences · 2024Article
- Methylation across the central dogma in health and diseases: new therapeutic strategies.Signal transduction and targeted therapy · 2023Review
- The immunomodulatory molecule TIGIT is expressed by chronic lymphocytic leukemia cells and contributes to anergy.Haematologica · 2023Article
- Immuno-regulatory malignant B cells contribute to Chronic Lymphocytic Leukemia progression.Cancer gene therapy · 2023Article
- Paradoxical activation of chronic lymphocytic leukemia cells by ruxolitinibFrontiers in oncology · 2023Article
- Regulation of S100As Expression by Inflammatory Cytokines in Chronic Lymphocytic Leukemia.International journal of molecular sciences · 2022Article
- Review
- Review
- Immunological and genetic kinetics from diagnosis to clinical progression in chronic lymphocytic leukemia.Biomarker research · 2021Article
- BTLA/HVEM Axis Induces NK Cell Immunosuppression and Poor Outcome in Chronic Lymphocytic Leukemia.Cancers · 2021Article
- IL10 hypomethylation is associated with the risk of gastric cancer.Oncology letters · 2021Article
- The Role of Janus Kinase/STAT3 Pathway in Hematologic Malignancies With an Emphasis on Epigenetics.Frontiers in genetics · 2021Review
- Celebrating 20 Years of IGHV Mutation Analysis in CLL.HemaSphere · 2020Review
- Epigenetic Changes Associated With Interleukin-10.Frontiers in immunology · 2020Review
- Increased autocrine interleukin-6 production is significantly associated with worse clinical outcome in patients with chronic lymphocytic leukemia.Journal of cellular physiology · 2019Article
- IgA levels at diagnosis predict for infections, time to treatment, and survival in chronic lymphocytic leukemia.Blood advances · 2019Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 3 countries.
Funding
Abstract
Chronic lymphocytic leukemias (CLLs) with unmutated (U-CLL) or mutated (M-CLL) IGHV have variable features of immunosuppression, possibly influenced by those CLL cells activated to produce interleukin 10 (IL-10). The two subsets differ in their levels of anergy, defined by low surface immunoglobulin M levels/signaling capacity, and in their DNA methylation profile, particularly variable in M-CLL. We have now found that levels of IL-10 produced by activated CLL cells were highly variable. Levels were higher in M-CLL than in U-CLL and correlated with anergy. DNA methylation analysis of IL10 locus revealed two previously uncharacterized 'variably methylated regions' (CLL-VMRs1/2) in the gene body, but similarly low methylation in the promoter of both U-CLL and M-CLL. CLL-VMR1/2 methylation was lower in M-CLL than in U-CLL and inversely correlated with IL-10 induction. A functional signal transducer and activator of transcription 3 (STAT3) binding site in CLL-VMR2 was confirmed by proximity ligation and luciferase assays, whereas inhibition of SYK-mediated STAT3 activation resulted in suppression of IL10. The data suggest epigenetic control of IL-10 production. Higher tumor load may compensate the reduced IL-10 production in U-CLL, accounting for clinical immunosuppression in both subsets. The observation that SYK inhibition also suppresses IL-10 provides a potential new rationale for therapeutic targeting and immunological rescue by SYK inhibitors in CLL.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.