ArticleCell death & disease2013
Cyclic AMP can promote APL progression and protect myeloid leukemia cells against anthracycline-induced apoptosis.
Article in Cell death & disease, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.
- Meta-analysis of gene signatures and key pathways indicates suppression of JNK pathway as a regulator of chemo-resistance in AML.Scientific reports · 2021Pooled it
- Regulatory Role of Zinc in Acute Promyelocytic Leukemia: Cellular and Molecular Aspects with Therapeutic Implications.International journal of molecular sciences · 2025Review
- Comprehensive analysis of phosducin-like 3 as a diagnostic, prognostic and immunological marker in pan-cancer.Frontiers in immunology · 2025Article
- Purine nucleosides replace cAMP in allosteric regulation of PKA in trypanosomatid pathogens.eLife · 2024Article
- cAMP-PKA/EPAC signaling and cancer: the interplay in tumor microenvironment.Journal of hematology & oncology · 2024Review
- Epigenetic changes in human model KMT2A leukemias highlight early events during leukemogenesis.Haematologica · 2022Article
- A forward genetic screen identifies modifiers of rocaglate responsiveness.Scientific reports · 2021Article
- Drug repurposing for targeting cyclic nucleotide transporters in acute leukemias - A missed opportunity.Seminars in cancer biology · 2021Review
- Forskolin Sensitizes Human Acute Myeloid Leukemia Cells to H3K27me2/3 Demethylases GSKJ4 Inhibitor via Protein Kinase A.Frontiers in pharmacology · 2018Article
- Cyclic AMP-Induced p53 Destabilization is Independent of CREB in Pre-B Acute Lymphoblastic Leukemia Cells.International journal of molecular and cellular medicine · 2016Article
- ADCY7 supports development of acute myeloid leukemia.Biochemical and biophysical research communications · 2015Article
- Active Pin1 is a key target of all-trans retinoic acid in acute promyelocytic leukemia and breast cancer.Nature medicine · 2015Article
- Elevation of cAMP Levels Inhibits Doxorubicin-Induced Apoptosis in Pre- B ALL NALM- 6 Cells Through Induction of BAD Phosphorylation and Inhibition of P53 Accumulation.International journal of molecular and cellular medicine · 2015Article
- Dual effect of oxidative stress on leukemia cancer induction and treatment.Journal of experimental & clinical cancer research : CR · 2014Review
- CREB-induced inflammation is important for malignant mesothelioma growth.The American journal of pathology · 2014Article
- Article
- Targeting protein kinase A in cancer therapy: an update.EXCLI journal · 2014Review
- Synthetic phosphoethanolamine has in vitro and in vivo anti-leukemia effects.British journal of cancer · 2013Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We show that cyclic AMP (cAMP) elevating agents protect blasts from patients with acute promyelocytic leukemia (APL) against death induced by first-line anti-leukemic anthracyclines like daunorubicin (DNR). The cAMP effect was reproduced in NB4 APL cells, and shown to depend on activation of the generally cytoplasmic cAMP-kinase type I (PKA-I) rather than the perinuclear PKA-II. The protection of both NB4 cells and APL blasts was associated with (inactivating) phosphorylation of PKA site Ser118 of pro-apoptotic Bad and (activating) phosphorylation of PKA site Ser133 of the AML oncogene CREB. Either event would be expected to protect broadly against cell death, and we found cAMP elevation to protect also against 2-deoxyglucose, rotenone, proteasome inhibitor and a BH3-only mimetic. The in vitro findings were mirrored by the findings in NSG mice with orthotopic NB4 cell leukemia. The mice showed more rapid disease progression when given cAMP-increasing agents (prostaglandin E2 analog and theophylline), both with and without DNR chemotherapy. The all-trans retinoic acid (ATRA)-induced terminal APL cell differentiation is a cornerstone in current APL treatment and is enhanced by cAMP. We show also that ATRA-resistant APL cells, believed to be responsible for treatment failure with current ATRA-based treatment protocols, were protected by cAMP against death. This suggests that the beneficial pro-differentiating and non-beneficial pro-survival APL cell effects of cAMP should be weighed against each other. The results suggest also general awareness toward drugs that can affect bone marrow cAMP levels in leukemia patients.
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Registered trials
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