ArticleThe Journal of experimental medicine2004
PML-RARA-RXR oligomers mediate retinoid and rexinoid/cAMP cross-talk in acute promyelocytic leukemia cell differentiation.
Article in The Journal of experimental medicine, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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Who cites it
63 citing papers in PubMed, 149 citations in OpenAlex.
- PML-driven sumoylation of PML::RARA-bound repressors drives hematopoietic progenitor immortalization.The Journal of experimental medicine · 2026Article
- Acute Promyelocytic Leukemia, Retinoic Acid, and Arsenic: A Tale of Dualities.Cold Spring Harbor perspectives in medicine · 2024Review
- PML::RARA and GATA2 proteins interact via DNA templates to induce aberrant self-renewal in mouse and human hematopoietic cells.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- History of Developing Acute Promyelocytic Leukemia Treatment and Role of Promyelocytic Leukemia Bodies.Cancers · 2024Review
- Multi-omics and machine learning reveal context-specific gene regulatory activities of PML::RARA in acute promyelocytic leukemia.Nature communications · 2023Article
- A Bioinformatics View on Acute Myeloid Leukemia Surface Molecules by Combined Bayesian and ABC Analysis.Bioengineering (Basel, Switzerland) · 2022Article
- History of Acute Promyelocytic Leukemia.Clinical hematology international · 2021Review
- Review
- Review
- Acute Promyelocytic Leukemia: A History over 60 Years-From the Most Malignant to the most Curable Form of Acute Leukemia.Oncology and therapy · 2019Review
- Article
- Differentiation therapy revisited.Nature reviews. Cancer · 2018Review
- NLS-RARα is a novel transcriptional factor.Oncology letters · 2017Article
- Superenhancer Analysis Defines Novel Epigenomic Subtypes of Non-APL AML, Including an RARα Dependency Targetable by SY-1425, a Potent and Selective RARα Agonist.Cancer discovery · 2017Article
- RXRα ligand Z-10 induces PML-RARα cleavage and APL cell apoptosis through disrupting PML-RARα/RXRα complex in a cAMP-independent manner.Oncotarget · 2017Article
- PML-RARA requires DNA methyltransferase 3A to initiate acute promyelocytic leukemia.The Journal of clinical investigation · 2016Article
- NLS-RARα Inhibits the Effects of All-trans Retinoic Acid on NB4 Cells by Interacting with P38α MAPK.International journal of medical sciences · 2016Article
- p53 as an Effector or Inhibitor of Therapy Response.Cold Spring Harbor perspectives in medicine · 2015Review
- Transcription and methylation analyses of preleukemic promyelocytes indicate a dual role for PML/RARA in leukemia initiation.Haematologica · 2015Article
- Transcriptional repression of CDKN2D by PML/RARα contributes to the altered proliferation and differentiation block of acute promyelocytic leukemia cells.Cell death & disease · 2014Article
3 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
PML-RARA was proposed to initiate acute promyelocytic leukemia (APL) through PML-RARA homodimer-triggered repression. Here, we examined the nature of the PML-RARA protein complex and of its DNA targets in APL cells. Using a selection/amplification approach, we demonstrate that PML-RARA targets consist of two AGGTCA elements in an astonishing variety of orientations and spacings, pointing to highly relaxed structural constrains for DNA binding and identifying a major gain of function of this oncogene. PML-RARA-specific response elements were identified, which all conveyed a major transcriptional response to RA only in APL cells. In these cells, we demonstrate that PML-RARA oligomers are complexed to RXR. Directly probing PML-RARA function in APL cells, we found that the differentiation enhancer cyclic AMP (cAMP) boosted transcriptional activation by RA. cAMP also reversed the normal silencing (subordination) of the transactivating function of RXR when bound to RARA or PML-RARA, demonstrating that the alternate rexinoid/cAMP-triggered APL differentiation pathway also activates PML-RARA targets. Finally, cAMP restored both RA-triggered differentiation and PML-RARA transcriptional activation in mutant RA-resistant APL cells. Collectively, our findings directly demonstrate that APL cell differentiation parallels transcriptional activation through PML-RARA-RXR oligomers and that those are functionally targeted by cAMP, identifying this agent as another oncogene-targeted therapy.
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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.