ArticleThe Journal of experimental medicine2021
Pathological RANK signaling in B cells drives autoimmunity and chronic lymphocytic leukemia.
Article in The Journal of experimental medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 20 citations in OpenAlex.
- Charge-based immunoreceptor signalling in health and disease.Nature reviews. Immunology · 2025Review
- The protective role of kakkalide in sepsis-induced intestinal barrier dysfunction via inhibition of NF-κB pathway activation.Journal of clinical biochemistry and nutrition · 2025Article
- Autoimmunity promotes chronic lymphocytic leukemia progression in an indolent disease model.Scientific reports · 2025Article
- Article
- B-cell intrinsic RANK signaling cooperates with TCL1 to induce lineage-dependent B-cell transformation.Blood cancer journal · 2024Article
- Mechanisms of gut homeostasis regulating Th17/Treg cell balance in PMOP.Frontiers in immunology · 2024Review
- Mouse models of chronic lymphocytic leukemia and Richter transformation: what we have learnt and what we are missing.Frontiers in immunology · 2024Review
- RANKL/RANK is required for cytokine-induced beta cell death; osteoprotegerin, a RANKL inhibitor, reverses rodent type 1 diabetes.Science advances · 2023Article
- Review
- Antibodies Produced by CLL Phenotype B Cells in Patients With Myasthenia Gravis Are Not Directed Against Neuromuscular Endplates.Neurology(R) neuroimmunology & neuroinflammation · 2023Article
- Safety and efficacy of canakinumab treatment for undifferentiated autoinflammatory diseases: the data of a retrospective cohort two-centered study.Frontiers in medicine · 2023Article
- Article
- RANKL biology.Bone · 2022Review
- Polygenic autoimmune disease risk alleles impacting B cell tolerance act in concert across shared molecular networks in mouse and in humans.Frontiers in immunology · 2022Review
- The Therapeutic Potential of Targeting NIK in B Cell Malignancies.Frontiers in immunology · 2022Review
- Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Clinical evidence suggests alterations in receptor activator of NF-κB (RANK) signaling are key contributors to B cell autoimmunity and malignancy, but the pathophysiological consequences of aberrant B cell-intrinsic RANK signaling remain unknown. We generated mice that express a human lymphoma-derived, hyperactive RANKK240E variant in B lymphocytes in vivo. Forced RANK signaling disrupted B cell tolerance and induced a fully penetrant systemic lupus erythematosus-like disease in addition to the development of chronic lymphocytic leukemia (CLL). Importantly, RANKK240E transgenic CLL cells as well as CLL cells of independent murine and of human origin depend on microenvironmental RANK ligand (RANKL) for tumor cell survival. Consequently, inhibition of the RANKL-RANK axis with anti-RANKL antibodies killed murine and human CLL cells in vitro and in vivo. These results establish pathological B cell-intrinsic RANK signaling as a potential driver of autoimmunity and B cell malignancy, and they suggest the exploitation of clinically available anti-RANKL compounds for CLL treatment.
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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 Socratic graph.