ArticleBlood2009
Rational combined targeting of phosphodiesterase 4B and SYK in DLBCL.
Article in Blood, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 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
25 citing papers in PubMed, 41 citations in OpenAlex.
- Trial
- First-Line Combination of R-CHOP with the PDE4 Inhibitor Roflumilast for High-Risk DLBCL.Cancers · 2024Article
- cAMP-PKA/EPAC signaling and cancer: the interplay in tumor microenvironment.Journal of hematology & oncology · 2024Review
- PDE4B promotes the progression of gastric cancer via the PI3K/AKT/MYC pathway and immune infiltration.American journal of cancer research · 2024Article
- Detecting Förster resonance energy transfer in living cells by conventional and spectral flow cytometry.Cytometry. Part A : the journal of the International Society for Analytical Cytology · 2022Article
- Article
- 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
- Generation and characterization of the Eµ-Irf8 mouse model.Cancer genetics · 2020Article
- MYC Regulation of D2HGDH and L2HGDH Influences the Epigenome and Epitranscriptome.Cell chemical biology · 2020Article
- PDE4 subtypes in cancer.Oncogene · 2020Review
- Article
- Synergistic Targeting of the Regulatory and Catalytic Subunits of PI3Kδ in Mature B-cell Malignancies.Clinical cancer research : an official journal of the American Association for Cancer Research · 2018Article
- Safety and Pharmacodynamics of the PDE4 Inhibitor Roflumilast in Advanced B-cell Malignancies.Clinical cancer research : an official journal of the American Association for Cancer Research · 2017Article
- Potential synergistic effect of phosphodiesterase inhibitors with chemotherapy in lung cancer.Journal of Cancer · 2017Article
- Review
- A phosphodiesterase 4B-dependent interplay between tumor cells and the microenvironment regulates angiogenesis in B-cell lymphoma.Leukemia · 2016Article
- Article
- D2HGDH regulates alpha-ketoglutarate levels and dioxygenase function by modulating IDH2.Nature communications · 2015Article
- Transcriptional analysis of apoptotic cerebellar granule neurons following rescue by gastric inhibitory polypeptide.International journal of molecular sciences · 2014Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Identification of rational therapeutic targets is an important strategy to improve the cure rate of diffuse large B-cell lymphoma (DLBCL). We previously showed that inhibition of the phosphodiesterase 4B (PDE4B) unleashes cyclic-AMP (cAMP) inhibitory effects toward the PI3K/AKT pathway and induces apoptosis. These data raised important considerations as to which upstream regulators mediate cAMP inhibition of PI3K/AKT, and how identifying this signaling route could be translated into clinical initiatives. We found that in normal and malignant B cells, cAMP potently inhibit the phosphorylation and activity of the tyrosine kinase SYK. Using genetic models of gain- and loss-of-function, we demonstrated the essential role for PDE4B in controlling these effects in DLBCL. Furthermore, we used a constitutively active SYK mutant to confirm its central role in transducing cAMP effects to PI3K/AKT. Importantly, given SYK credentials as a therapeutic target in B-cell tumors, we explored the role of PDE4B in these responses. In multiple DLBCL models, we found that genetically, hence specifically, inhibiting PDE4B expression significantly improved the efficacy of SYK inhibitors. Our data defined a hitherto unknown role for cAMP in negatively regulating SYK and indicate that combined inhibition of PDE4B and SYK should be actively pursued.
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What OpenQuestion holds
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.