ArticleInternational journal of cancer2017
Activation of the B-cell receptor successively activates NF-κB and STAT3 in chronic lymphocytic leukemia cells.
Article in International journal of cancer, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 56 citations in OpenAlex.
- Article
- Article
- Non-canonical transcriptional regulation of the poor prognostic factor UGT2B17 in chronic lymphocytic leukemic and normal B cells.BMC cancer · 2024Article
- B cell receptor signaling and associated pathways in the pathogenesis of chronic lymphocytic leukemia.Frontiers in oncology · 2024Review
- The immunomodulatory molecule TIGIT is expressed by chronic lymphocytic leukemia cells and contributes to anergy.Haematologica · 2023Article
- New insights into the Lck-NF-κB signaling pathway.Frontiers in cell and developmental biology · 2023Review
- miR-29b-3p suppresses the malignant biological behaviors of AML cells via inhibiting NF-κB and JAK/STAT signaling pathways by targeting HuR.BMC cancer · 2022Article
- The Pt(International journal of molecular sciences · 2022Article
- Shikonin Derivatives fromNutrients · 2021Article
- HELQ and EGR3 expression correlate with IGHV mutation status and prognosis in chronic lymphocytic leukemia.Journal of translational medicine · 2021Article
- Targeting Janus Kinases and Signal Transducer and Activator of Transcription 3 to Treat Inflammation, Fibrosis, and Cancer: Rationale, Progress, and Caution.Pharmacological reviews · 2020Review
- Clinico-Biological Implications of Modified Levels of Cytokines in Chronic Lymphocytic Leukemia: A Possible Therapeutic Role.Cancers · 2020Review
- Article
- Article
- Article
- STAT3 promotes chronic lymphocytic leukemia progression through upregulating SMYD3 expression.Archives of medical science : AMS · 2019Article
- Increased autocrine interleukin-6 production is significantly associated with worse clinical outcome in patients with chronic lymphocytic leukemia.Journal of cellular physiology · 2019Article
- The Antidiabetic and Antinephritic Activities ofOxidative medicine and cellular longevity · 2018Article
Corrections and comments
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Authors and funding
13 authors at 1 institution in 2 countries.
Funding
Abstract
In chronic lymphocytic leukemia (CLL) cells, both interleukin-6 (IL-6) and the B-cell receptor (BCR) activate Janus kinase 2 (JAK2) and induce the phosphorylation of signal transduction and activator of transcription 3 (STAT3) on tyrosine 705 residues. However, whereas IL-6 phosphorylates STAT3 within 15 min, stimulation of the BCR with anti-immunoglobulin M (IgM) antibodies phosphorylates STAT3 in 2-4 hr. Here, we show that this process takes longer because it requires transcriptional activity of NF-κB. Using an electromobility shift assay, we found that incubation with IgM antibodies for 4 or 18 hr, but not 15 min, increased NF-κB DNA-binding of CLL cells and increased binding was translated to increased transcriptional activity. Hence, 42% of the 83 NF-κB target genes were constitutively expressed in all CLL cells prior to any inducible stimuli. However, activation of the BCR increased the number of NF-κB target genes with detectable expression by 23%. Remarkably, prolonged incubation with anti-IgM antibodies induced a time-dependent transcription, production and secretion of IL-6 protein. The IgM-induced production of IL-6 prompted the phosphorylation of STAT3 on tyrosine residues. This effect was inhibited by the JAK1/2 inhibitor of the JAK/STAT3 pathway ruxolitinib. Taken together, these results suggest that in CLL cells, constitutive tonic activation of NF-κB can be further enhanced by the BCR and that the BCR-induced activation of the JAK/STAT3 pathway depends on the NF-κB induced production of IL-6.
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