ArticleLeukemia2000
A mutated PML/RARA found in the retinoid maturation resistant NB4 subclone, NB4-R2, blocks RARA and wild-type PML/RARA transcriptional activities.
Article in Leukemia, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 77 citations in OpenAlex.
- Tumor suppressor-like mutations mark a dosage-constrained dependency in leukemia.bioRxiv : the preprint server for biology · 2026Article
- ZIP10 as a potential therapeutic target in acute myeloid leukaemia.British journal of haematology · 2025Article
- A novel network pharmacology approach for leukaemia differentiation therapy using MogrifyOncogene · 2022Article
- STMN1 is highly expressed and contributes to clonogenicity in acute promyelocytic leukemia cells.Investigational new drugs · 2022Article
- Low HOX gene expression in PML-RARα-positive leukemia results from suppressed histone demethylation.Epigenetics · 2018Article
- Antagonism between granulocytic maturation and deacetylase inhibitor-induced apoptosis in acute promyelocytic leukaemia cells.British journal of cancer · 2015Article
- Retinoic acid synergizes ATO-mediated cytotoxicity by precluding Nrf2 activity in AML cells.British journal of cancer · 2014Article
- WIPI-dependent autophagy during neutrophil differentiation of NB4 acute promyelocytic leukemia cells.Cell death & disease · 2014Article
- Combined staurosporine and retinoic acid induces differentiation in retinoic acid resistant acute promyelocytic leukemia cell lines.Scientific reports · 2014Article
- HOX antisense lincRNA HOXA-AS2 is an apoptosis repressor in all trans retinoic acid treated NB4 promyelocytic leukemia cells.Journal of cellular biochemistry · 2013Article
- Mechanisms of action and resistance to all-trans retinoic acid (ATRA) and arsenic trioxide (As2O 3) in acute promyelocytic leukemia.International journal of hematology · 2013Review
- Inhibition of mitotic kinase Aurora suppresses Akt-1 activation and induces apoptotic cell death in all-trans retinoid acid-resistant acute promyelocytic leukemia cells.Journal of translational medicine · 2011Article
- Article
- A myelopoiesis-associated regulatory intergenic noncoding RNA transcript within the human HOXA cluster.Blood · 2009Article
- Dissection of mechanisms of Chinese medicinal formula Realgar-Indigo naturalis as an effective treatment for promyelocytic leukemia.Proceedings of the National Academy of Sciences of the United States of America · 2008Article
- Arginine methylation provides epigenetic transcription memory for retinoid-induced differentiation in myeloid cells.Molecular and cellular biology · 2005Article
- An antagonist of retinoic acid receptors more effectively inhibits growth of human prostate cancer cells than normal prostate epithelium.British journal of cancer · 2004Article
- PML-RARA-RXR oligomers mediate retinoid and rexinoid/cAMP cross-talk in acute promyelocytic leukemia cell differentiation.The Journal of experimental medicine · 2004Article
- Arsenic enhances the activation of Stat1 by interferon gamma leading to synergistic expression of IRF-1.Oncogene · 2003Article
- Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The fusion protein PML/RARA, associated with acute promyelocytic leukemia behaves as an abnormal retinoic acid (RA) receptor with altered transactivation properties but is still inducible by RA. The chimeric protein is thought to promote leukemogenesis but also paradoxically to mediate the sensitivity to ATRA of APL cells. This has been supported by works reporting that in vitro ATRA resistance is characterized by defects in the RARA/E-domain of PML/RARA. In the present report, we identified a new mutation in the E domain of PML/RARA which is associated with a RA-resistant subline of NB4 cells; NB4-R2. This mutation, identical to the Gln411 mutation found in HL60-R, changes the amino acid Gln903 to an in-phase stop codon, generating a truncated form of PML/RARA which has lost 52 amino acids at its C-terminal end. We have studied the effect of the truncated PML/RARA protein on PML NB formation and RARA and PML/RARA transcriptional activity. We show here that the fusion mutant exerts a dominant negative effect on wild-type PML, PML/RARA and RARA transcription activity. These findings highlight the important role of the RARA E-domain of PML/RARA in mediating RA sensitivity in APL cells.
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