ArticleOncogene2017
Myc enhances B-cell receptor signaling in precancerous B cells and confers resistance to Btk inhibition.
Article in Oncogene, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 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
28 citing papers in PubMed, 38 citations in OpenAlex.
- Trial
- Fat Mass and Obesity-Associated Protein Contributes to Tumorigenesis and Drug Resistance of Diffuse Large B-Cell Lymphoma by Suppressing N6-Methyladenosine Methylation of Myc.The Kaohsiung journal of medical sciences · 2026Article
- RHEBL1 expression is activated by the Oct4-Sox2 complex in oral squamous cell carcinoma.Functional & integrative genomics · 2026Article
- Signaling pathways and targeted interventions for precancers.Signal transduction and targeted therapy · 2026Review
- MIZ-1 controls transcriptional programs required for BCR signaling, actin dynamics, and naïve B cell survival.Frontiers in immunology · 2026Article
- Zanubrutinib-based regimen as the salvage or bridging treatment of CART therapy in relapsed or refractory, non-germinal center B-cell-like diffuse large B-cell lymphoma: a retrospective multicenter cohort study.Frontiers in immunology · 2026Observational
- B-cell receptor signaling and microenvironment crosstalk in mantle cell lymphoma.Cell communication and signaling : CCS · 2025Review
- Exploring the potential of Buzhong Yiqi decoction in the treatment of membranous nephropathy: a comprehensive study combining bioinformatics, network pharmacology, and experimental validation.American journal of translational research · 2025Article
- DOCK8 gene mutation alters cell subsets, BCR signaling, and cell metabolism in B cells.Cell death & disease · 2024Article
- Review
- Intracellular Flow Cytometry ("Phosphoflow") to Assess Signal Transduction in Rare Populations Such As Memory B Cell Subsets and Plasma Cells.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Phosphoflow cytometry to assess cytokine signaling pathways in peripheral immune cells: potential for inferring immune cell function and treatment response in patients with solid tumors.Journal of experimental & clinical cancer research : CR · 2023Review
- Identification and Biological Evaluation of a Water-Soluble Fullerene Nanomaterial as BTK Kinase Inhibitor.International journal of nanomedicine · 2023Article
- Targeting MYC-driven lymphoma: lessons learned and future directions.Cancer drug resistance (Alhambra, Calif.) · 2023Review
- A Novel Triple-Action Inhibitor Targeting B-Cell Receptor Signaling and BRD4 Demonstrates Preclinical Activity in Chronic Lymphocytic Leukemia.International journal of molecular sciences · 2022Article
- Bruton's tyrosine kinase inhibition induces rewiring of proximal and distal B-cell receptor signaling in mice.European journal of immunology · 2021Article
- MYC: a multipurpose oncogene with prognostic and therapeutic implications in blood malignancies.Journal of hematology & oncology · 2021Review
- Overcoming of Microenvironment Protection on Primary Chronic Lymphocytic Leukemia Cells after Treatment with BTK and MDM2 Pharmacological Inhibitors.Current oncology (Toronto, Ont.) · 2021Article
- Non-Coding RNAs: The "Dark Side Matter" of the CLL Universe.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Aberrantly expressed Bruton's tyrosine kinase preferentially drives metastatic and stem cell-like phenotypes in neuroblastoma cells.Cellular oncology (Dordrecht, Netherlands) · 2020Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Dysregulation of the oncogenic transcription factor MYC induces B-cell transformation and is a driver for B-cell non-Hodgkin lymphoma (B-NHL). MYC overexpression in B-NHL is associated with more aggressive phenotypes and poor prognosis. Although genomic studies suggest a link between MYC overexpression and B-cell receptor (BCR) signaling molecules in B-NHL, signaling pathways essential to Myc-mediated B-cell transformation have not been fully elucidated. We utilized intracellular phospho-flow cytometry to investigate the relationship between Myc and BCR signaling in pre-malignant B cells. Utilizing the Eμ-myc mouse model, where Myc is overexpressed specifically in B cells, both basal and stimulated BCR signaling were increased in precancerous B lymphocytes from Eμ-myc mice compared with wild-type littermates. B cells overexpressing Myc displayed constitutively higher levels of activated CD79α, Btk, Plcγ2 and Erk1/2. Notably, Myc-overexpressing B cells maintained elevated BCR signaling despite treatment with ibrutinib, a Bruton's tyrosine kinase inhibitor. Furthermore, PI3K/Akt pathway signaling was also increased in Eμ-myc B cells, and this increase was partially suppressed with ibrutinib. In addition, experiments with Btk-null B cells revealed off-target effects of ibrutinib on BCR signaling. Our data show that in pre-malignant B cells, Myc overexpression is sufficient to activate BCR and PI3K/Akt signaling pathways and further enhances signaling following BCR ligation. Therefore, our results indicate that precancerous B cells have already acquired enhanced survival and growth capabilities before transformation, and that elevated MYC levels confer resistance to pharmacologic inhibitors of BCR signaling, which has significant implications for B-NHL 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 OpenQuestion graph.