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RUNX1-ETO and RUNX1-EVI1 Differentially Reprogram the Chromatin Landscape in t(8;21) and t(3;21) AML
Acute myeloid leukemia (AML) is a heterogeneous disease caused by mutations in transcriptional regulator genes, but how different mutant regulators shape the chromatin landscape is unclear. Here, we compared the transcriptional networks of two types of AML with chromosomal translocations of the RUNX...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cell Press
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5457485/ https://www.ncbi.nlm.nih.gov/pubmed/28538183 http://dx.doi.org/10.1016/j.celrep.2017.05.005 |
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author | Loke, Justin Assi, Salam A. Imperato, Maria Rosaria Ptasinska, Anetta Cauchy, Pierre Grabovska, Yura Soria, Natalia Martinez Raghavan, Manoj Delwel, H. Ruud Cockerill, Peter N. Heidenreich, Olaf Bonifer, Constanze |
author_facet | Loke, Justin Assi, Salam A. Imperato, Maria Rosaria Ptasinska, Anetta Cauchy, Pierre Grabovska, Yura Soria, Natalia Martinez Raghavan, Manoj Delwel, H. Ruud Cockerill, Peter N. Heidenreich, Olaf Bonifer, Constanze |
author_sort | Loke, Justin |
collection | PubMed |
description | Acute myeloid leukemia (AML) is a heterogeneous disease caused by mutations in transcriptional regulator genes, but how different mutant regulators shape the chromatin landscape is unclear. Here, we compared the transcriptional networks of two types of AML with chromosomal translocations of the RUNX1 locus that fuse the RUNX1 DNA-binding domain to different regulators, the t(8;21) expressing RUNX1-ETO and the t(3;21) expressing RUNX1-EVI1. Despite containing the same DNA-binding domain, the two fusion proteins display distinct binding patterns, show differences in gene expression and chromatin landscape, and are dependent on different transcription factors. RUNX1-EVI1 directs a stem cell-like transcriptional network reliant on GATA2, whereas that of RUNX1-ETO-expressing cells is more mature and depends on RUNX1. However, both types of AML are dependent on the continuous expression of the fusion proteins. Our data provide a molecular explanation for the differences in clinical prognosis for these types of AML. |
format | Online Article Text |
id | pubmed-5457485 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Cell Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-54574852017-06-09 RUNX1-ETO and RUNX1-EVI1 Differentially Reprogram the Chromatin Landscape in t(8;21) and t(3;21) AML Loke, Justin Assi, Salam A. Imperato, Maria Rosaria Ptasinska, Anetta Cauchy, Pierre Grabovska, Yura Soria, Natalia Martinez Raghavan, Manoj Delwel, H. Ruud Cockerill, Peter N. Heidenreich, Olaf Bonifer, Constanze Cell Rep Article Acute myeloid leukemia (AML) is a heterogeneous disease caused by mutations in transcriptional regulator genes, but how different mutant regulators shape the chromatin landscape is unclear. Here, we compared the transcriptional networks of two types of AML with chromosomal translocations of the RUNX1 locus that fuse the RUNX1 DNA-binding domain to different regulators, the t(8;21) expressing RUNX1-ETO and the t(3;21) expressing RUNX1-EVI1. Despite containing the same DNA-binding domain, the two fusion proteins display distinct binding patterns, show differences in gene expression and chromatin landscape, and are dependent on different transcription factors. RUNX1-EVI1 directs a stem cell-like transcriptional network reliant on GATA2, whereas that of RUNX1-ETO-expressing cells is more mature and depends on RUNX1. However, both types of AML are dependent on the continuous expression of the fusion proteins. Our data provide a molecular explanation for the differences in clinical prognosis for these types of AML. Cell Press 2017-05-23 /pmc/articles/PMC5457485/ /pubmed/28538183 http://dx.doi.org/10.1016/j.celrep.2017.05.005 Text en © 2017 The Author(s) http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Loke, Justin Assi, Salam A. Imperato, Maria Rosaria Ptasinska, Anetta Cauchy, Pierre Grabovska, Yura Soria, Natalia Martinez Raghavan, Manoj Delwel, H. Ruud Cockerill, Peter N. Heidenreich, Olaf Bonifer, Constanze RUNX1-ETO and RUNX1-EVI1 Differentially Reprogram the Chromatin Landscape in t(8;21) and t(3;21) AML |
title | RUNX1-ETO and RUNX1-EVI1 Differentially Reprogram the Chromatin Landscape in t(8;21) and t(3;21) AML |
title_full | RUNX1-ETO and RUNX1-EVI1 Differentially Reprogram the Chromatin Landscape in t(8;21) and t(3;21) AML |
title_fullStr | RUNX1-ETO and RUNX1-EVI1 Differentially Reprogram the Chromatin Landscape in t(8;21) and t(3;21) AML |
title_full_unstemmed | RUNX1-ETO and RUNX1-EVI1 Differentially Reprogram the Chromatin Landscape in t(8;21) and t(3;21) AML |
title_short | RUNX1-ETO and RUNX1-EVI1 Differentially Reprogram the Chromatin Landscape in t(8;21) and t(3;21) AML |
title_sort | runx1-eto and runx1-evi1 differentially reprogram the chromatin landscape in t(8;21) and t(3;21) aml |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5457485/ https://www.ncbi.nlm.nih.gov/pubmed/28538183 http://dx.doi.org/10.1016/j.celrep.2017.05.005 |
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