ArticleThe Journal of experimental medicine2002
In vivo activation of cAMP signaling induces growth arrest and differentiation in acute promyelocytic leukemia.
Article in The Journal of experimental medicine, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 98 citations in OpenAlex.
- Expression of ABCC-type nucleotide exporters in blasts of adult acute myeloid leukemia: relation to long-term survival.Clinical cancer research : an official journal of the American Association for Cancer Research · 2009Trial
- Activation of orphan receptor GPR132 induces cell differentiation in acute myeloid leukemia.Cell death & disease · 2022Article
- Fatty acid oxidation is a druggable gateway regulating cellular plasticity for driving metastasis in breast cancer.Science advances · 2021Article
- Disparate roles of retinoid acid signaling molecules in kidney disease.American journal of physiology. Renal physiology · 2021Review
- PRMT1 inhibition induces differentiation of colon cancer cells.Scientific reports · 2020Article
- Combination of enzastaurin and ATRA exerts dose-dependent dual effects on ATRA-resistant acute promyelocytic leukemia cells.American journal of cancer research · 2019Article
- Differentiation therapy revisited.Nature reviews. Cancer · 2018Review
- Inhibition of Phosphodiesterase 5 and Increasing the Level of Cyclic Guanosine 3',5' Monophosphate by HydroalcoholicBreast cancer : basic and clinical research · 2017Article
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- Multidrug resistance protein 4/ ATP binding cassette transporter 4: a new potential therapeutic target for acute myeloid leukemia.Oncotarget · 2014Article
- Growth arrest and forced differentiation of human primary glioblastoma multiforme by a novel small molecule.Scientific reports · 2014Article
- MicroRNA-181a-mediated downregulation of AC9 protein decreases intracellular cAMP level and inhibits ATRA-induced APL cell differentiation.Cell death & disease · 2014Article
- Synergy against PML-RARa: targeting transcription, proteolysis, differentiation, and self-renewal in acute promyelocytic leukemia.The Journal of experimental medicine · 2013Review
- Uncoupling RARA transcriptional activation and degradation clarifies the bases for APL response to therapies.The Journal of experimental medicine · 2013Article
- How animal models of leukaemias have already benefited patients.Molecular oncology · 2013Review
- Cyclic AMP can promote APL progression and protect myeloid leukemia cells against anthracycline-induced apoptosis.Cell death & disease · 2013Article
- 8-CPT-cAMP/all-trans retinoic acid targets t(11;17) acute promyelocytic leukemia through enhanced cell differentiation and PLZF/RARα degradation.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Inhibition of phosphodiestrase 9 induces cGMP accumulation and apoptosis in human breast cancer cell lines, MCF-7 and MDA-MB-468.Cell proliferation · 2012Article
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- Review
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Differentiation therapy for acute myeloid leukemia uses transcriptional modulators to reprogram cancer cells. The most relevant clinical example is acute promyelocytic leukemia (APL), which responds dramatically to either retinoic acid (RA) or arsenic trioxide (As(2)O(3)). In many myeloid leukemia cell lines, cyclic adenosine monophosphate (cAMP) triggers growth arrest, cell death, or differentiation, often in synergy with RA. Nevertheless, the toxicity of cAMP derivatives and lack of suitable models has hampered trials designed to assess the in vivo relevance of theses observations. We show that, in an APL cell line, cAMP analogs blocked cell growth and unraveled As(2)O(3)-triggered differentiation. Similarly, in RA-sensitive or RA-resistant mouse models of APL, continuous infusions of 8-chloro-cyclic adenosine monophosphate (8-Cl-cAMP) triggered major growth arrest, greatly enhanced both spontaneous and RA- or As(2)O(3)-induced differentiation and accelerated the restoration of normal hematopoiesis. Theophylline, a well-tolerated phosphodiesterase inhibitor which stabilizes endogenous cAMP, also impaired APL growth and enhanced spontaneous or As(2)O(3)-triggered cell differentiation in vivo. Accordingly, in an APL patient resistant to combined RA-As(2)O(3) therapy, theophylline induced blast clearance and restored normal hematopoiesis. Taken together, these results demonstrate that in vivo activation of cAMP signaling contributes to APL clearance, independently of its RA-sensitivity, thus raising hopes that other myeloid leukemias may benefit from this therapeutic approach.
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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.