ArticleBlood2020
Targeting chronic NFAT activation with calcineurin inhibitors in diffuse large B-cell lymphoma.
Article in Blood, 2020. 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, 32 citations in OpenAlex.
- NFATc1 and NFATc2 regulate glucocorticoid resistance in pediatric T-cell acute lymphoblastic leukemia through modulation of cholesterol biosynthesis and the WNT/β-catenin pathway.Haematologica · 2026Article
- Synergistic roles of NFATc1 and c-Jun in immunomodulation.Biochemistry and biophysics reports · 2025Review
- Molecular Pathways and Targeted Therapies in Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL).Cancers · 2025Review
- FcRL1, a New B-Cell-Activating Co-Receptor.International journal of molecular sciences · 2025Review
- Acidosis regulates immune progression in rheumatoid arthritis by promoting the expression of cytokines and co-stimulatory molecules in synovial fibroblasts.Molecular medicine (Cambridge, Mass.) · 2025Article
- Advancements in pharmacological interventions for atopic dermatitis current strategies and future directions.Inflammopharmacology · 2025Review
- Article
- Engineering a solution for allogeneic CAR-T rejection.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Advances in biology, diagnosis and treatment of DLBCL.Annals of hematology · 2024Review
- Glucocorticoids paradoxically promote steroid resistance in B cell acute lymphoblastic leukemia through CXCR4/PLC signaling.Nature communications · 2024Article
- Calcineurin Is a Universal Regulator of Vessel Function-Focus on Vascular Smooth Muscle Cells.Cells · 2023Review
- Calcineurin-mediated dephosphorylation enhances the stability and transactivation of c-Myc.Scientific reports · 2023Article
- The oncogenic fusion protein DNAJB1-PRKACA can be specifically targeted by peptide-based immunotherapy in fibrolamellar hepatocellular carcinoma.Nature communications · 2022Article
- NFAT1 Orchestrates Spinal Microglial Transcription and Promotes Microglial Proliferation via c-MYC Contributing to Nerve Injury-Induced Neuropathic Pain.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- Targeting MYC and BCL2 by a natural compound for "double-hit" lymphoma.Hematological oncology · 2022Article
- Calcineurin in development and disease.Genes & diseases · 2022Review
- Article
- Hypoxia-induced NFATc3 deSUMOylation enhances pancreatic carcinoma progression.Cell death & disease · 2022Article
- RNA-seq and integrated network analysis reveals the hub genes and key pathway of paclitaxel inhibition on Adriamycin resistant diffuse large B cell lymphoma cells.Bioengineered · 2022Article
- Deregulated calcium signaling in blood cancer: Underlying mechanisms and therapeutic potential.Frontiers in oncology · 2022Review
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Authors and funding
16 authors at 6 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Diffuse large B-cell lymphoma (DLBCL) represents the most common adult lymphoma and can be divided into 2 major molecular subtypes: the germinal center B-cell-like and the aggressive activated B-cell-like (ABC) DLBCL. Previous studies suggested that chronic B-cell receptor signaling and increased NF-κB activation contribute to ABC DLBCL survival. Here we show that the activity of the transcription factor NFAT is chronically elevated in both DLBCL subtypes. Surprisingly, NFAT activation is independent of B-cell receptor signaling, but mediated by an increased calcium flux and calcineurin-mediated dephosphorylation of NFAT. Intriguingly, although NFAT is activated in both DLBCL subtypes, long-term calcineurin inhibition with cyclosporin A or FK506, both clinically approved drugs, triggers potent cytotoxicity specifically in ABC DLBCL cells. The antitumor effects of calcineurin inhibitors are associated with the reduced expression of c-Jun, interleukin-6, and interleukin-10, which were identified as NFAT target genes that are particularly important for the survival of ABC DLBCL. Furthermore, calcineurin blockade synergized with BCL-2 and MCL-1 inhibitors in killing ABC DLBCL cells. Collectively, these findings identify constitutive NFAT signaling as a crucial functional driver of ABC DLBCL and highlight calcineurin inhibition as a novel strategy for the treatment of this aggressive lymphoma subtype.
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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.