AML associated oncofusion proteins PML-RARA, AML1-ETO and CBFB-MYH11 target RUNX/ETS-factor binding sites to modulate H3ac levels and drive leukemogenesis

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Singh , A A , Mandoli , A , Prange , K H M , Laakso , M & Martens , J H A 2017 , ' AML associated oncofusion proteins PML-RARA, AML1-ETO and CBFB-MYH11 target RUNX/ETS-factor binding sites to modulate H3ac levels and drive leukemogenesis ' , Oncotarget , vol. 8 , no. 8 , pp. 12855-12865 . https://doi.org/10.18632/oncotarget.14150

Title: AML associated oncofusion proteins PML-RARA, AML1-ETO and CBFB-MYH11 target RUNX/ETS-factor binding sites to modulate H3ac levels and drive leukemogenesis
Author: Singh, Abhishek A.; Mandoli, Amit; Prange, Koen H. M.; Laakso, Marko; Martens, Joost H. A.
Other contributor: University of Helsinki, Research Programs Unit


Date: 2017
Language: eng
Number of pages: 11
Belongs to series: Oncotarget
ISSN: 1949-2553
DOI: https://doi.org/10.18632/oncotarget.14150
URI: http://hdl.handle.net/10138/180174
Abstract: Chromosomal translocations are one of the hallmarks of acute myeloid leukemia (AML), often leading to gene fusions and expression of an oncofusion protein. Over recent years it has become clear that most of the AML associated oncofusion proteins molecularly adopt distinct mechanisms for inducing leukemogenesis. Still these unique molecular properties of the chimeric proteins converge and give rise to a common pathogenic molecular mechanism. In the present study we compared genome-wide DNA binding and transcriptome data associated with AML1-ETO, CBFB-MYH11 and PML-RARA oncofusion protein expression to identify unique and common features. Our analyses revealed targeting of oncofusion binding sites to RUNX1 and ETS-factor occupied genomic regions. In addition, it revealed a highly comparable global histone acetylation pattern, similar expression of common target genes and related enrichment of several biological pathways critical for maintenance of AML, suggesting oncofusion proteins deregulate common gene programs despite their distinct binding signatures and mechanisms of action.
Subject: AML
PML-RARA
AML1-ETO
CBFB-MYH11
RUNX1
ACUTE MYELOID-LEUKEMIA
ACUTE PROMYELOCYTIC LEUKEMIA
TRANS-RETINOIC ACID
GENE-EXPRESSION
CANCER-THERAPY
1ST RELAPSE
ACETYLATION
INHIBITORS
TRANSLOCATIONS
PREDICTION
3122 Cancers
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