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| Item Type: | Article |
|---|---|
| Title: | MYB induces the expression of the oncogenic corepressor SKI in acute myeloid leukemia |
| Creators Name: | Frech, M. and Teichler, S. and Feld, C. and Bouchard, C. and Berberich, H. and Sorg, K. and Mernberger, M. and Bullinger, L. and Bauer, U.M. and Neubauer, A. |
| Abstract: | Acute myeloid leukemia (AML) arises through clonal expansion of transformed myeloid progenitor cells. The 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 gene in AML cells. Reporter gene assays using MYB binding sites present in the gene locus show MYB-dependent transcriptional activation. SiRNA-mediated depletion of in leukemic cell lines reveals that MYB is crucial for gene expression. Consistently, we observed a positive correlation of and expression in leukemic cell lines and in samples of AML patients. Moreover, and both were downregulated by treatment with histone deacetylase inhibitors. Strikingly, differentiation of AML cells induced by depletion of MYB is attenuated by overexpression of . Our findings identify SKI as a novel MYB target gene, relevant for the MYB-induced differentiation block in leukemic cells. |
| Keywords: | Oncogene, MYB, SKI, Transcriptional Regulation, Acute Myeloid Leukemia |
| Source: | Oncotarget |
| ISSN: | 1949-2553 |
| Publisher: | Impact Journals |
| Volume: | 9 |
| Number: | 32 |
| Page Range: | 22423-22435 |
| Date: | 27 April 2018 |
| Official Publication: | https://doi.org/10.18632/oncotarget.25051 |
| PubMed: | View item in PubMed |
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