ArticleLeukemia2016
A phosphodiesterase 4B-dependent interplay between tumor cells and the microenvironment regulates angiogenesis in B-cell lymphoma.
Article in Leukemia, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 65 citations in OpenAlex.
- Personalized Combination Therapy in Bladder Cancer: cAMP Modulators Synergize with 5-FU and Modulate Redox Programs.Cancers · 2026Article
- α-Ketoglutarate promotes amino acid depletion and suppresses B-cell lymphoma growth and development.Blood · 2025Article
- The multifaceted role of phosphodiesterase 4 in tumor: from tumorigenesis to immunotherapy.Frontiers in immunology · 2025Review
- First-Line Combination of R-CHOP with the PDE4 Inhibitor Roflumilast for High-Risk DLBCL.Cancers · 2024Article
- Hypoxia promotes histone H3K9 lactylation to enhanceiScience · 2024Article
- IRF8-mutant B cell lymphoma evades immunity through a CD74-dependent deregulation of antigen processing and presentation in MHCII complexes.Science advances · 2024Article
- PDE4B promotes the progression of gastric cancer via the PI3K/AKT/MYC pathway and immune infiltration.American journal of cancer research · 2024Article
- PDE4 Phosphodiesterases in Cardiovascular Diseases: Key Pathophysiological Players and Potential Therapeutic Targets.International journal of molecular sciences · 2023Review
- Article
- The Complexity and Multiplicity of the Specific cAMP Phosphodiesterase Family: PDE4, Open New Adapted Therapeutic Approaches.International journal of molecular sciences · 2022Review
- Diffuse large B-cell lymphoma and new insights into its pathobiology and implication in treatment.Journal of family medicine and primary care · 2022Review
- The Endothelial Activation and Stress Index (EASIX) score is an independent prognostic factor in patients with diffuse large B-cell lymphoma.BMC cancer · 2022Article
- Article
- Article
- Clinical Implication of Phosphodiesterase-4-Inhibition.International journal of molecular sciences · 2022Review
- Role of Roflumilast Combined with ESHAP Chemotherapy in Relapsed/Refractory Patients with Diffuse Large B-Cell Lymphoma.Cancer research and treatment · 2022Article
- Cyclic adenosine monophosphate/phosphodiesterase 4 pathway associated with immune infiltration and PD-L1 expression in lung adenocarcinoma cells.Frontiers in oncology · 2022Article
- The regulatory role of PDE4B in the progression of inflammatory function study.Frontiers in pharmacology · 2022Review
- Regulation of PD-L1 expression is a novel facet of cyclic-AMP-mediated immunosuppression.Leukemia · 2021Article
- Berberine ameliorates vascular dysfunction by a global modulation of lncRNA and mRNA expression profiles in hypertensive mouse aortae.PloS one · 2021Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Angiogenesis associates with poor outcome in diffuse large B-cell lymphoma (DLBCL), but the contribution of the lymphoma cells to this process remains unclear. Addressing this knowledge gap may uncover unsuspecting proangiogenic signaling nodes and highlight alternative antiangiogenic therapies. Here, we identify the second messenger cyclic-AMP (cAMP) and the enzyme that terminates its activity, phosphodiesterase 4B (PDE4B), as regulators of B-cell lymphoma angiogenesis. We first show that cAMP, in a PDE4B-dependent manner, suppresses PI3K/AKT signals to downmodulate vascular endothelial growth factor (VEGF) secretion and vessel formation in vitro. Next, we create a novel mouse model that combines the lymphomagenic Myc transgene with germline deletion of Pde4b. We show that lymphomas developing in a Pde4b-null background display significantly lower microvessel density (MVD) in association with lower VEGF levels and PI3K/AKT activity. We recapitulate these observations by treating lymphoma-bearing mice with the FDA-approved PDE4 inhibitor, Roflumilast. Lastly, we show that primary human DLBCLs with high PDE4B expression display significantly higher MVD. Here, we defined an unsuspected signaling circuitry in which the cAMP generated in lymphoma cells downmodulates PI3K/AKT and VEGF secretion to negatively influence vessel development in the microenvironment. These data identify PDE4 as an actionable antiangiogenic target in DLBCL.
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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.