The Hematopoietic Transcription Factors RUNX1 and ERG Prevent AML1-ETO Oncogene Overexpression and Onset of the Apoptosis Program in t(8;21) AMLs.

Abstract:

:The t(8;21) acute myeloid leukemia (AML)-associated oncoprotein AML1-ETO disrupts normal hematopoietic differentiation. Here, we have investigated its effects on the transcriptome and epigenome in t(8,21) patient cells. AML1-ETO binding was found at promoter regions of active genes with high levels of histone acetylation but also at distal elements characterized by low acetylation levels and binding of the hematopoietic transcription factors LYL1 and LMO2. In contrast, ERG, FLI1, TAL1, and RUNX1 bind at all AML1-ETO-occupied regulatory regions, including those of the AML1-ETO gene itself, suggesting their involvement in regulating AML1-ETO expression levels. While expression of AML1-ETO in myeloid differentiated induced pluripotent stem cells (iPSCs) induces leukemic characteristics, overexpression increases cell death. We find that expression of wild-type transcription factors RUNX1 and ERG in AML is required to prevent this oncogene overexpression. Together our results show that the interplay of the epigenome and transcription factors prevents apoptosis in t(8;21) AML cells.

journal_name

Cell Rep

journal_title

Cell reports

authors

Mandoli A,Singh AA,Prange KHM,Tijchon E,Oerlemans M,Dirks R,Ter Huurne M,Wierenga ATJ,Janssen-Megens EM,Berentsen K,Sharifi N,Kim B,Matarese F,Nguyen LN,Hubner NC,Rao NA,van den Akker E,Altucci L,Vellenga E,Stunnenb

doi

10.1016/j.celrep.2016.08.082

subject

Has Abstract

pub_date

2016-11-15 00:00:00

pages

2087-2100

issue

8

issn

2211-1247

pii

S2211-1247(16)31178-0

journal_volume

17

pub_type

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