ArticleOncotarget2016
Cyclic AMP efflux inhibitors as potential therapeutic agents for leukemia.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
15 citing papers in PubMed, 20 citations in OpenAlex.
- Identification of novelTherapeutic advances in hematology · 2026Article
- Chemotherapeutic and Antiproliferative Effect of Purified Protein from Marine Catfish Tachysurus Dussumieri on Human Colon Cancer Cell Line.Cell biochemistry and biophysics · 2024Article
- Specific MRP4 Inhibitor Ceefourin-1 Enhances Apoptosis Induced by 6-Mercaptopurine in Jurkat Leukemic Cells, but Not in Normal Lymphoblast Cell Line CRL-1991.Medicina (Kaunas, Lithuania) · 2022Article
- Epigenetic changes in human model KMT2A leukemias highlight early events during leukemogenesis.Haematologica · 2022Article
- Study of Endogen Substrates, Drug Substrates and Inhibitors Binding Conformations on MRP4 and Its Variants by Molecular Docking and Molecular Dynamics.Molecules (Basel, Switzerland) · 2021Article
- Review
- Drug repurposing for targeting cyclic nucleotide transporters in acute leukemias - A missed opportunity.Seminars in cancer biology · 2021Review
- Regulating cellular cyclic adenosine monophosphate: "Sources," "sinks," and now, "tunable valves".Wiley interdisciplinary reviews. Systems biology and medicine · 2020Review
- VLA-4 Expression and Activation in B Cell Malignancies: Functional and Clinical Aspects.International journal of molecular sciences · 2020Review
- Clioquinol: To harm or heal.Pharmacology & therapeutics · 2019Review
- Forskolin exerts anticancer roles in non-Hodgkin's lymphomas via regulating Axin/β-catenin signaling pathway.Cancer management and research · 2019Article
- Pharmacological modulation of the COPharmacology & therapeutics · 2018Review
- High-Throughput Flow Cytometry Drug Combination Discovery with Novel Synergy Analysis Software, SynScreen.SLAS discovery : advancing life sciences R & D · 2018Article
- High-Throughput Flow Cytometry Identifies Small-Molecule Inhibitors for Drug Repurposing in T-ALL.SLAS discovery : advancing life sciences R & D · 2018Article
- Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Apoptotic evasion is a hallmark of cancer. We propose that some cancers may evade cell death by regulating 3'-5'-cyclic adenosine monophosphate (cAMP), which is associated with pro-apoptotic signaling. We hypothesize that leukemic cells possess mechanisms that efflux cAMP from the cytoplasm, thus protecting them from apoptosis. Accordingly, cAMP efflux inhibition should result in: cAMP accumulation, activation of cAMP-dependent downstream signaling, viability loss, and apoptosis. We developed a novel assay to assess cAMP efflux and performed screens to identify inhibitors. In an acute myeloid leukemia (AML) model, several identified compounds reduced cAMP efflux, appropriately modulated pathways that are responsive to cAMP elevation (cAMP-responsive element-binding protein phosphorylation, and deactivation of Very Late Antigen-4 integrin), and induced mitochondrial depolarization and caspase activation. Blocking adenylyl cyclase activity was sufficient to reduce effects of the most potent compounds. These compounds also decreased cAMP efflux and viability of B-lineage acute lymphoblastic leukemia (B-ALL) cell lines and primary patient samples, but not of normal primary peripheral blood mononuclear cells. Our data suggest that cAMP efflux is a functional feature that could be therapeutically targeted in leukemia. Furthermore, because some of the identified drugs are currently used for treating other illnesses, this work creates an opportunity for repurposing.
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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.