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

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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.

In: Cell Reports, Vol. 19, No. 8, 23.05.2017, p. 1654-1668.

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@article{e9e7a019941c496faa9a9f26d8268772,
title = "RUNX1-ETO and RUNX1-EVI1 Differentially Reprogram the Chromatin Landscape in t(8;21) and t(3;21) AML",
abstract = "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.",
keywords = "RUNX1-EVI1, RUNX1-ETO, epigenetic landscape, chromatin, transcriptional network, acute myeloid leukemia",
author = "Justin Loke and Assi, {Salam A} and Imperato, {Maria Rosaria} and Anetta Ptasinska and Pierre Cauchy and Yura Grabovska and Soria, {Natalia Martinez} and Manoj Raghavan and Delwel, {H Ruud} and Cockerill, {Peter N} and Olaf Heidenreich and Constanze Bonifer",
note = "Copyright {\textcopyright} 2017 The Author(s). Published by Elsevier Inc. All rights reserved.",
year = "2017",
month = may,
day = "23",
doi = "10.1016/j.celrep.2017.05.005",
language = "English",
volume = "19",
pages = "1654--1668",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Elsevier",
number = "8",

}

RIS

TY - JOUR

T1 - RUNX1-ETO and RUNX1-EVI1 Differentially Reprogram the Chromatin Landscape in t(8;21) and t(3;21) AML

AU - Loke, Justin

AU - Assi, Salam A

AU - Imperato, Maria Rosaria

AU - Ptasinska, Anetta

AU - Cauchy, Pierre

AU - Grabovska, Yura

AU - Soria, Natalia Martinez

AU - Raghavan, Manoj

AU - Delwel, H Ruud

AU - Cockerill, Peter N

AU - Heidenreich, Olaf

AU - Bonifer, Constanze

N1 - Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

PY - 2017/5/23

Y1 - 2017/5/23

N2 - 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.

AB - 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.

KW - RUNX1-EVI1

KW - RUNX1-ETO

KW - epigenetic landscape

KW - chromatin

KW - transcriptional network

KW - acute myeloid leukemia

U2 - 10.1016/j.celrep.2017.05.005

DO - 10.1016/j.celrep.2017.05.005

M3 - Article

C2 - 28538183

VL - 19

SP - 1654

EP - 1668

JO - Cell Reports

JF - Cell Reports

SN - 2211-1247

IS - 8

ER -