Oncotarget

Research Papers:

MYB induces the expression of the oncogenic corepressor SKI in acute myeloid leukemia

Miriam Frech, Sabine Teichler, Christine Feld, Caroline Bouchard, Hannah Berberich, Katharina Sorg, Marco Mernberger, Lars Bullinger, Uta-Maria Bauer and Andreas Neubauer _

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Oncotarget. 2018; 9:22423-22435. https://doi.org/10.18632/oncotarget.25051

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Abstract

Miriam Frech1,2,*, Sabine Teichler1,2,*, Christine Feld1,2,3,*, Caroline Bouchard3, Hannah Berberich3, Katharina Sorg1,2, Marco Mernberger4, Lars Bullinger5, Uta-Maria Bauer3 and Andreas Neubauer1,2

1Department of Internal Medicine and Hematology, Oncology and Immunology, Philipps University Marburg, Marburg 35033, Germany

2University Hospital Giessen and Marburg, Marburg 35033, Germany

3Institute of Molecular Biology and Tumor Research (IMT), School of Medicine, Philipps University Marburg, Marburg 35043, Germany

4Institute of Molecular Oncology, Philipps University Marburg, Marburg 35043, Germany

5Department of Internal Medicine III, University Hospital of Ulm, Ulm 89081, Germany

*These authors contributed equally to this work

Correspondence to:

Andreas Neubauer, email: neubauer@staff.uni-marburg.de

Keywords: oncogene; MYB; SKI; transcriptional regulation; acute myeloid leukemia

Received: July 26, 2017     Accepted: March 21, 2018     Published: April 27, 2018

ABSTRACT

Acute myeloid leukemia (AML) arises through clonal expansion of transformed myeloid progenitor cells. The SKI proto-oncogene is highly upregulated in different solid tumors and leukemic cells, but little is known about its transcriptional regulation during leukemogenesis. MYB is an important hematopoietic transcription factor involved in proliferation as well as differentiation and upregulated in most human acute leukemias. Here, we find that MYB protein binds within the regulatory region of the SKI gene in AML cells. Reporter gene assays using MYB binding sites present in the SKI gene locus show MYB-dependent transcriptional activation. SiRNA-mediated depletion of MYB in leukemic cell lines reveals that MYB is crucial for SKI gene expression. Consistently, we observed a positive correlation of MYB and SKI expression in leukemic cell lines and in samples of AML patients. Moreover, MYB and SKI both were downregulated by treatment with histone deacetylase inhibitors. Strikingly, differentiation of AML cells induced by depletion of MYB is attenuated by overexpression of SKI. Our findings identify SKI as a novel MYB target gene, relevant for the MYB-induced differentiation block in leukemic cells.


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