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

Justin Loke, Salam A. Assi, Maria Rosaria Imperato, Anetta Ptasinska, Pierre Cauchy, Yura Grabovska, Natalia Martinez Soria, Manoj Raghavan, H. Ruud Delwel, Peter N. Cockerill, Olaf Heidenreich, Constanze Bonifer

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

32 Citaten (Scopus)

Samenvatting

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.

Originele taal-2Engels
Pagina's (van-tot)1654-1668
Aantal pagina's15
TijdschriftCell Reports
Volume19
Nummer van het tijdschrift8
DOI's
StatusGepubliceerd - 23 mei 2017
Extern gepubliceerdJa

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