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AML1/ETO and its function as a regulator of gene transcription via epigenetic mechanisms
The chromosomal translocation t(8;21) and the resulting oncofusion gene AML1/ETO have long served as a prototypical genetic lesion to model and understand leukemogenesis. In this review, we describe the wide-ranging role of AML1/ETO in AML leukemogenesis, with a particular focus on the aberrant epig...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8460439/ https://www.ncbi.nlm.nih.gov/pubmed/34331016 http://dx.doi.org/10.1038/s41388-021-01952-w |
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author | Rejeski, Kai Duque-Afonso, Jesús Lübbert, Michael |
author_facet | Rejeski, Kai Duque-Afonso, Jesús Lübbert, Michael |
author_sort | Rejeski, Kai |
collection | PubMed |
description | The chromosomal translocation t(8;21) and the resulting oncofusion gene AML1/ETO have long served as a prototypical genetic lesion to model and understand leukemogenesis. In this review, we describe the wide-ranging role of AML1/ETO in AML leukemogenesis, with a particular focus on the aberrant epigenetic regulation of gene transcription driven by this AML-defining mutation. We begin by analyzing how structural changes secondary to distinct genomic breakpoints and splice changes, as well as posttranscriptional modifications, influence AML1/ETO protein function. Next, we characterize how AML1/ETO recruits chromatin-modifying enzymes to target genes and how the oncofusion protein alters chromatin marks, transcription factor binding, and gene expression. We explore the specific impact of these global changes in the epigenetic network facilitated by the AML1/ETO oncofusion on cellular processes and leukemic growth. Furthermore, we define the genetic landscape of AML1/ETO-positive AML, presenting the current literature concerning the incidence of cooperating mutations in genes such as KIT, FLT3, and NRAS. Finally, we outline how alterations in transcriptional regulation patterns create potential vulnerabilities that may be exploited by epigenetically active agents and other therapeutics. |
format | Online Article Text |
id | pubmed-8460439 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-84604392021-10-07 AML1/ETO and its function as a regulator of gene transcription via epigenetic mechanisms Rejeski, Kai Duque-Afonso, Jesús Lübbert, Michael Oncogene Review Article The chromosomal translocation t(8;21) and the resulting oncofusion gene AML1/ETO have long served as a prototypical genetic lesion to model and understand leukemogenesis. In this review, we describe the wide-ranging role of AML1/ETO in AML leukemogenesis, with a particular focus on the aberrant epigenetic regulation of gene transcription driven by this AML-defining mutation. We begin by analyzing how structural changes secondary to distinct genomic breakpoints and splice changes, as well as posttranscriptional modifications, influence AML1/ETO protein function. Next, we characterize how AML1/ETO recruits chromatin-modifying enzymes to target genes and how the oncofusion protein alters chromatin marks, transcription factor binding, and gene expression. We explore the specific impact of these global changes in the epigenetic network facilitated by the AML1/ETO oncofusion on cellular processes and leukemic growth. Furthermore, we define the genetic landscape of AML1/ETO-positive AML, presenting the current literature concerning the incidence of cooperating mutations in genes such as KIT, FLT3, and NRAS. Finally, we outline how alterations in transcriptional regulation patterns create potential vulnerabilities that may be exploited by epigenetically active agents and other therapeutics. Nature Publishing Group UK 2021-07-30 2021 /pmc/articles/PMC8460439/ /pubmed/34331016 http://dx.doi.org/10.1038/s41388-021-01952-w Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Review Article Rejeski, Kai Duque-Afonso, Jesús Lübbert, Michael AML1/ETO and its function as a regulator of gene transcription via epigenetic mechanisms |
title | AML1/ETO and its function as a regulator of gene transcription via epigenetic mechanisms |
title_full | AML1/ETO and its function as a regulator of gene transcription via epigenetic mechanisms |
title_fullStr | AML1/ETO and its function as a regulator of gene transcription via epigenetic mechanisms |
title_full_unstemmed | AML1/ETO and its function as a regulator of gene transcription via epigenetic mechanisms |
title_short | AML1/ETO and its function as a regulator of gene transcription via epigenetic mechanisms |
title_sort | aml1/eto and its function as a regulator of gene transcription via epigenetic mechanisms |
topic | Review Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8460439/ https://www.ncbi.nlm.nih.gov/pubmed/34331016 http://dx.doi.org/10.1038/s41388-021-01952-w |
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