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RUNX1-ETO and RUNX1-EVI1 Differentially Reprogram the Chromatin Landscape in t(8;21) and t(3;21) AML

Lookup NU author(s): Yura Grabovska, Professor Olaf Heidenreich

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

© 2017 The Author(s) 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.


Publication metadata

Author(s): Loke J, Assi SA, Imperato MR, Ptasinska A, Cauchy P, Grabovska Y, Soria NM, Raghavan M, Delwel HR, Cockerill PN, Heidenreich O, Bonifer C

Publication type: Article

Publication status: Published

Journal: Cell Reports

Year: 2017

Volume: 19

Issue: 8

Pages: 1654-1668

Online publication date: 23/05/2017

Acceptance date: 28/04/2017

ISSN (electronic): 2211-1247

Publisher: Elsevier BV

URL: https://doi.org/10.1016/j.celrep.2017.05.005

DOI: 10.1016/j.celrep.2017.05.005


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