Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/98199
Citations | ||
Scopus | Web of Science® | Altmetric |
---|---|---|
?
|
?
|
Type: | Journal article |
Title: | Hypoxia inducible factor (HIF)-2α accelerates disease progression in mouse models of leukemia and lymphoma but is not a poor prognosis factor in human AML |
Other Titles: | Hypoxia inducible factor (HIF)-2alpha accelerates disease progression in mouse models of leukemia and lymphoma but is not a poor prognosis factor in human AML |
Author: | Forristal, C.E. Brown, A.L. Helwani, F.M. Winkler, I.G. Nowlan, B. Barbier, V. Powell, R. Engler, G.A. Diakiw, S. Zannettino, A.C.W. Martin, S. Pattabiraman, D. D'Andrea, R.J. Lewis, I.D. Levesque, J.P. |
Citation: | Leukemia, 2015; 29(10):2075-2085 |
Publisher: | Nature Publishing Group |
Issue Date: | 2015 |
ISSN: | 0887-6924 1476-5551 |
Statement of Responsibility: | C E Forristal, A L Brown, F M Helwani, I G Winkler, B Nowlan, V Barbier, R J Powell, G A Engler, S M Diakiw, A C W Zannettino, S Martin, D Pattabiraman, R J D'Andrea, I D Lewis and J P Levesque |
Abstract: | Hypoxia-inducible factor (HIF)-1α accumulation promotes hematopoietic stem cells' quiescence and is necessary to maintain their self-renewal. However, the role of HIF-2α in hematopoietic cells is less clear. We investigated the role of HIF-2α in leukemia and lymphoma cells. HIF-2α expression was high in subsets of human and mouse leukemia and lymphoma cells, whereas it was low in normal bone marrow leukocytes. To investigate the role of HIF-2α, we transduced human HIF-2α cDNA in mouse syngeneic models of myeloid preleukemia and a transgenic model of B lymphoma. Ectopic expression of HIF-2α accelerated leukemia cell proliferation in vitro. Mice transplanted with cells transduced with HIF-2α died significantly faster of leukemia or B lymphoma than control mice transplanted with empty vector-transduced cells. Conversely, HIF-2α knockdown in human myeloid leukemia HL60 cells decreased proliferation in vitro and significantly prolonged animal survival following transplantation. In human acute myeloid leukemia (AML), HIF-2α mRNA was significantly elevated in several subsets such as the t(15;17), inv(16), complex karyotype and favorable cytogenetic groups. However, patients with high HIF-2α expression had a trend to higher disease-free survival in univariate analysis. The different effects of HIF-2α overexpression in mouse models of leukemia and human AML illustrates the complexity of this mutliclonal disease. |
Keywords: | Real-Time Polymerase Chain Reaction |
Description: | Published online 15 May 2015 |
Rights: | © 2015 Macmillan Publishers Limited All rights reserved |
DOI: | 10.1038/leu.2015.102 |
Grant ID: | http://purl.org/au-research/grants/nhmrc/604303 http://purl.org/au-research/grants/nhmrc/1044091 http://purl.org/au-research/grants/nhmrc/1033736 http://purl.org/au-research/grants/nhmrc/488821 |
Published version: | http://dx.doi.org/10.1038/leu.2015.102 |
Appears in Collections: | Aurora harvest 3 Medicine publications |
Files in This Item:
There are no files associated with this item.
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.