ArticleProceedings of the National Academy of Sciences of the United States of America2007
RARalpha-PLZF overcomes PLZF-mediated repression of CRABPI, contributing to retinoid resistance in t(11;17) acute promyelocytic leukemia.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 69 citations in OpenAlex.
- CRABP1 Signalosomes in Non-Canonical Actions of Retinoic Acid-Maintaining Health and Preventing Thyroid Dysfunction in Aging.Endocrines · 2025Article
- Review
- Function of PML-RARA in Acute Promyelocytic Leukemia.Advances in experimental medicine and biology · 2024Review
- Differentiation therapy using low-dose venetoclax in a variant acute promyelocytic leukaemia carrying ZBTB16-RARA.British journal of haematology · 2022Article
- The MYCN inhibitor BGA002 restores the retinoic acid response leading to differentiation or apoptosis by the mTOR block in MYCN-amplified neuroblastoma.Journal of experimental & clinical cancer research : CR · 2022Article
- Review
- Current views on the genetic landscape and management of variant acute promyelocytic leukemia.Biomarker research · 2021Review
- Review
- PLZF-RARCancers · 2020Review
- Review
- Genetics and functions of the retinoic acid pathway, with special emphasis on the eye.Human genomics · 2019Review
- Acute Promyelocytic Leukemia: Update on the Mechanisms of Leukemogenesis, Resistance and on Innovative Treatment Strategies.Cancers · 2019Review
- Review
- The role of zinc and its compounds in leukemia.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2018Review
- Eya2, a Target Activated by Plzf, Is Critical forMolecular and cellular biology · 2017Article
- Review
- Post transcriptional control of the epigenetic stem cell regulator PLZF by sirtuin and HDAC deacetylases.Epigenetics & chromatin · 2015Article
- Activation of a promyelocytic leukemia-tumor protein 53 axis underlies acute promyelocytic leukemia cure.Nature medicine · 2014Article
- RARα-PLZF oncogene inhibits C/EBPα function in myeloid cells.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- The epigenetic regulator PLZF represses L1 retrotransposition in germ and progenitor cells.The EMBO journal · 2013Article
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Authors and funding
13 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Leukemia-associated chimeric oncoproteins often act as transcriptional repressors, targeting promoters of master genes involved in hematopoiesis. We show that CRABPI (encoding cellular retinoic acid binding protein I) is a target of PLZF, which is fused to RARalpha by the t(11;17)(q23;q21) translocation associated with retinoic acid (RA)-resistant acute promyelocytic leukemia (APL). PLZF represses the CRABPI locus through propagation of chromatin condensation from a remote intronic binding element culminating in silencing of the promoter. Although the canonical, PLZF-RARalpha oncoprotein has no impact on PLZF-mediated repression, the reciprocal translocation product RARalpha-PLZF binds to this remote binding site, recruiting p300, inducing promoter hypomethylation and CRABPI gene up-regulation. In line with these observations, RA-resistant murine PLZF/RARalpha+RARalpha/PLZF APL blasts express much higher levels of CRABPI than standard RA-sensitive PML/RARalpha APL. RARalpha-PLZF confers RA resistance to a retinoid-sensitive acute myeloid leukemia (AML) cell line in a CRABPI-dependent fashion. This study supports an active role for PLZF and RARalpha-PLZF in leukemogenesis, identifies up-regulation of CRABPI as a mechanism contributing to retinoid resistance, and reveals the ability of the reciprocal fusion gene products to mediate distinct epigenetic effects contributing to the leukemic phenotype.
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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.