ArticleClinical cancer research : an official journal of the American Association for Cancer Research2012
Quantitative immunofluorescence reveals the signature of active B-cell receptor signaling in diffuse large B-cell lymphoma.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 47 citations in OpenAlex.
- Tumor-associated B-cells induce tumor heterogeneity and therapy resistance.Nature communications · 2017Trial
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- Society for Immunotherapy of Cancer: Standards for Reporting of Multiplex Immunohistochemistry/Immunofluorescence Assays (STORMI).Journal for immunotherapy of cancer · 2025Article
- Genomic and Immunophenotypic Landscape of Acquired Resistance to PD-(L)1 Blockade in Non-Small-Cell Lung Cancer.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2024Article
- B-Cell Receptor Signaling and Beyond: The Role of Igα (CD79a)/Igβ (CD79b) in Normal and Malignant B Cells.International journal of molecular sciences · 2023Review
- Impact of TMB/PD-L1 expression and pneumonitis on chemoradiation and durvalumab response in stage III NSCLC.Nature communications · 2023Article
- Dissecting the clinicopathologic, genomic, and immunophenotypic correlates of KRASAnnals of oncology : official journal of the European Society for Medical Oncology · 2022Article
- Oncogenic Mutations in the DNA-Binding Domain of FOXO1 that Disrupt Folding: Quantitative Insights from Experiments and Molecular Simulations.Biochemistry · 2022Article
- Efficient automatic 3D segmentation of cell nuclei for high-content screening.BMC bioinformatics · 2022Article
- Low peripheral blood derived neutrophil-to-lymphocyte ratio (dNLR) is associated with increased tumor T-cell infiltration and favorable outcomes to first-line pembrolizumab in non-small cell lung cancer.Journal for immunotherapy of cancer · 2021Article
- The value of circulating microRNAs for early diagnosis of B-cell lymphoma: A case-control study on historical samples.Scientific reports · 2020Article
- PD-L1 over-expression is driven by B-cell receptor signaling in diffuse large B-cell lymphoma.Laboratory investigation; a journal of technical methods and pathology · 2019Article
- Outcomes of patients with relapsed/refractory double-expressor B-cell lymphoma treated with ibrutinib monotherapy.Blood advances · 2019Article
- Article
- Effective Combination Therapies for B-cell Lymphoma Predicted by a Virtual Disease Model.Cancer research · 2017Article
- Article
- Rapid 3-D delineation of cell nuclei for high-content screening platforms.Computers in biology and medicine · 2016Article
- [Advances of aberrant signaling pathways and related targeting drugs in B cell non- Hodgkin lymphoma].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2015Article
- Increased SYK activity is associated with unfavorable outcome among patients with acute myeloid leukemia.Oncotarget · 2015Article
- Optimized Near-IR Fluorescent Agents for in Vivo Imaging of Btk Expression.Bioconjugate chemistry · 2015Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
purposeB-cell receptor (BCR)-mediated signaling is important in the pathogenesis of a subset of diffuse large B-cell lymphomas (DLBCL) and the BCR-associated kinases SYK and BTK have recently emerged as potential therapeutic targets. We sought to identify a signature of activated BCR signaling in DLBCL to aid the identification of tumors that may be most likely to respond to BCR-pathway inhibition. EXPERIMENTAL
designWe applied quantitative immunofluorescence (qIF) using antibodies to phosphorylated forms of proximal BCR signaling kinases LYN, SYK, and BTK and antibody to BCR-associated transcription factor FOXO1 on BCR-cross-linked formalin-fixed paraffin-embedded (FFPE) DLBCL cell lines as a model system and on two clinical cohorts of FFPE DLBCL specimens (n = 154).
resultsA robust signature of active BCR signaling was identified and validated in BCR-cross-linked DLBCL cell lines and in 71/154 (46%) of the primary DLBCL patient specimens. Further analysis of the primary biopsy samples revealed increased nuclear exclusion of FOXO1 among DLBCL with qIF evidence of active BCR signaling compared with those without (P = 0.004). Nuclear exclusion of FOXO1 was also detected in a subset of DLBCL without evidence of proximal BCR signaling suggesting that alternative mechanisms for PI3K/AKT activation may mediate FOXO1 subcellular localization in these cases.
conclusionThis study establishes the feasibility of detecting BCR activation in primary FFPE biopsy specimens of DLBCL. It lays a foundation for future dissection of signal transduction networks in DLBCL and provides a potential platform for evaluating individual tumors in patients receiving novel therapies targeting the BCR pathway.
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