ArticleOncotarget2016
Interferon regulatory factor 4 attenuates Notch signaling to suppress the development of chronic lymphocytic leukemia.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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The trial behind it
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
13 citing papers in PubMed, 18 citations in OpenAlex.
- Somatic Recombination Between an Ancient and a RecentInternational journal of molecular sciences · 2024Article
- B-1a Cells, but Not Marginal Zone B Cells, Are Implicated in the Accumulation of Autoreactive Plasma Cells in Lyn-/- Mice.ImmunoHorizons · 2024Article
- Reduced IRF4 expression promotes lytic phenotype in Type 2 EBV-infected B cells.PLoS pathogens · 2022Article
- E3 Ubiquitin Ligase Regulators of Notch Receptor Endocytosis: From Flies to Humans.Biomolecules · 2022Review
- Role of Notch2 pathway in mature B cell malignancies.Frontiers in oncology · 2022Review
- Emerging roles of the HECT-type E3 ubiquitin ligases in hematological malignancies.Discover oncology · 2021Review
- Mouse Models in the Study of Mature B-Cell Malignancies.Cold Spring Harbor perspectives in medicine · 2021Review
- Notch2 Increases the Resistance to Venetoclax-Induced Apoptosis in Chronic Lymphocytic Leukemia B Cells by Inducing Mcl-1.Frontiers in oncology · 2021Article
- Targeting Nuclear NOTCH2 by Gliotoxin Recovers a Tumor-Suppressor NOTCH3 Activity in CLL.Cells · 2020Article
- SYK kinase mediates brown fat differentiation and activation.Nature communications · 2017Article
- Interferon regulatory factor 4 (IRF4) is overexpressed in human non‑small cell lung cancer (NSCLC) and activates the Notch signaling pathway.Molecular medicine reports · 2017Article
- Article
- Chronic lymphocytic leukaemia.Nature reviews. Disease primers · 2017Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Molecular pathogenesis of Chronic Lymphocytic Leukemia (CLL) is not fully elucidated. Genome wide association studies have linked Interferon Regulatory Factor 4 (IRF4) to the development of CLL. We recently established a causal relationship between low levels of IRF4 and development of CLL. However, the molecular mechanism through which IRF4 suppresses CLL development remains unclear. Deregulation of Notch signaling pathway has been identified as one of the most recurrent molecular anomalies in the pathogenesis of CLL. Yet, the role of Notch signaling as well as its regulation during CLL development remains poorly understood. Previously, we demonstrated that IRF4 deficient mice expressing immunoglobulin heavy chain Vh11 (IRF4-/-Vh11) developed spontaneous CLL with complete penetrance. In this study, we show that elevated Notch2 expression and the resulting hyperactivation of Notch signaling are common features of IRF4-/-Vh11 CLL cells. Our studies further reveal that Notch signaling is indispensable for CLL development in the IRF4-/-Vh11 mice. Moreover, we identify E3 ubiquitin ligase Nedd4, which targets Notch for degradation, as a direct target of IRF4 in CLL cells and their precursors. Collectively, our studies provide the first in vivo evidence for an essential role of Notch signaling in the development of CLL and establish IRF4 as a critical regulator of Notch signaling during CLL development.
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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.