Lookup NU author(s): Yura Grabovska,
Professor Olaf Heidenreich
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 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.
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
Online publication date: 23/05/2017
Acceptance date: 28/04/2017
ISSN (electronic): 2211-1247
Publisher: Elsevier BV
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