Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/82428
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Type: | Journal article |
Title: | Hoxa9 regulated Bcl-2 expression mediates survival of myeloid progenitors and the severity of Hoxa9-dependent leukemia |
Author: | Brumatti, G. Salmanidis, M. Kok, C. Bilardi, R. Sandow, J. Silke, N. Mason, K. Visser, J. Jabbour, A. Glaser, S. Okamoto, T. Bouillet, P. D'Andrea, R. Ekert, P. |
Citation: | Oncotarget, 2013; 4(11):1933-1947 |
Publisher: | Impact Journals LLC |
Issue Date: | 2013 |
ISSN: | 1949-2553 1949-2553 |
Statement of Responsibility: | Gabriela Brumatti, Marika Salmanidis, Chung H Kok, Rebecca A Bilardi, Jarrod J Sandow, Natasha Silke, Kylie Mason, Jolanda Visser, Anissa M Jabbour, Stefan P Glaser, Toru Okamoto, Philippe Bouillet, Richard J D'Andrea, and Paul G Ekert |
Abstract: | Deregulated expression of Hox genes such as HoxA9 is associated with development of myeloproliferative disorders and leukemia and indicates a poor prognosis. To investigate the molecular mechanisms by which HoxA9 promotes immortalization of hematopoietic cells, we generated growth factor dependent myeloid cells in which HoxA9 expression is regulated by administration of 4-hydroxy-tamoxifen. Maintenance of HoxA9 overexpression is required for continued cell survival and proliferation, even in the presence of growth factors. We show for the first time that maintenance of Bcl-2 expression is critical for HoxA9-dependent immortalization and influences the latency of HoxA9-dependent leukemia. Hematopoietic cells lacking Bcl-2 were not immortalized by HoxA9 in vitro. Furthermore, deletion of Bcl-2 delayed the onset and reduced the severity of HoxA9/Meis1 and MLL-AF9 leukemias. This is the first description of a molecular link between HoxA9 and the regulation of Bcl-2 family members in acute myeloid leukemia. |
Keywords: | HoxA9, Bcl-2, Leukemia, apoptosis |
Rights: | © 2013 Brumatti et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited |
DOI: | 10.18632/oncotarget.1306 |
Grant ID: | NHMRC |
Published version: | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3875760/ |
Appears in Collections: | Aurora harvest 4 Medicine publications |
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hdl_82428.pdf | Published version | 4.31 MB | Adobe PDF | View/Open |
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