ArticleClinical and translational medicine2022
Single-cell profiling-guided combination therapy of c-Fos and histone deacetylase inhibitors in diffuse large B-cell lymphoma.
Article in Clinical and translational medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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12 citing papers in PubMed, 22 citations in OpenAlex.
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- Transcriptomic profiling in canine B-cell lymphoma supports a synergistic effect of BTK and PI3K inhibitors.Frontiers in veterinary science · 2025Article
- Single-cell sequencing analysis of multiple myeloma heterogeneity and identification of new theranostic targets.Cell death & disease · 2024Article
- Rupatadine-inhibited OTUD3 promotes DLBCL progression and immune evasion through deubiquitinating MYL12A and PD-L1.Cell death & disease · 2024Article
- Metabolic imbalance driving immune cell phenotype switching in autoimmune disorders: Tipping the balance of T- and B-cell interactions.Clinical and translational medicine · 2024Article
- m6A-Modified circTET2 Interacting with HNRNPC Regulates Fatty Acid Oxidation to Promote the Proliferation of Chronic Lymphocytic Leukemia.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Advances in single-cell RNA sequencing and its applications in cancer research.Journal of hematology & oncology · 2023Review
- An In Vitro Antimicrobial, Anticancer and Antioxidant Activity ofMolecules (Basel, Switzerland) · 2023Article
- Single-cell profiling guided combination therapy of c-Fos and histone deacetylase inhibitors in diffuse large B-cell lymphoma.Clinical and translational medicine · 2022Article
- Single-cell profiling-guided combination therapy of c-Fos and histone deacetylase inhibitors in diffuse large B-cell lymphoma.Clinical and translational medicine · 2022Article
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundDiffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma. Histone deacetylase inhibitors (HDACis) have been widely applied in multiple tumours, but the expected efficacy was not observed in DLBCL. Therefore, this study is aimed to explore superior HDACis and optimise a relative combinational therapeutic strategy.
methodsThe antitumour effects of the drug were evaluated by Cell Counting Kit-8 (CCK-8) assay and apoptosis analysis. Single-cell RNA sequencing (scRNA-Seq) was used to analyse the intratumoural heterogeneity of DLBCL cells. Whole-exome sequencing and RNA sequencing were performed to analyse the genetic and transcriptional features. Western blotting, qRT-PCR, protein array, immunohistochemistry, and chromatin immunoprecipitation assays were applied to explore the involved pathways. The antitumour effects of the compounds were assessed using subcutaneous xenograft tumour models.
resultsLAQ824 was screened and confirmed to kill DLBCL cells effectively. Using scRNA-Seq, we characterised the heterogeneity of DLBCL cells under different drug pressures, and c-Fos was identified as a critical factor in the survival of residual tumour cells. Moreover, we demonstrated that combinatorial treatment with LAQ824 and a c-Fos inhibitor more potently inhibited tumour cells both in vitro and in vivo.
conclusionAltogether, we found an HDACi, LAQ824, with high efficacy in DLBCL and provided a promising HDACi-based combination therapy strategy.
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