HoxA9 regulated Bcl-2 expression mediates survival of myeloid progenitors and the severity of HoxA9-dependent leukemia.
- Brumatti, G; Salmanidis, M; Kok, CH; Bilardi, RA; Sandow, JJ; Silke, N; Mason, K; Visser, J; Jabbour, AM; Glaser, SP; Okamoto, T; Bouillet, P; D'Andrea, RJ; Ekert, PG;
Publication Year 2013-09-15, Volume 4, Issue #11, Page 1933-1947
- Journal Title
- Publication Type
- JOURNAL ARTICLE
- 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.
- Impact Journals LLC
- HoxA9 ; Bcl-2 ; Leukemia ; apoptosis
- WEHI Research Division(s)
- Cell Signalling And Cell Death; Cancer And Haematology; Molecular Genetics Of Cancer
- Open Access at Publisher's Site
- Rights Notice
- 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.
Creation Date: 2013-09-15 12:00:00Last Modified: 0001-01-01 12:00:00