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

Forristal, C. E., Brown, A. L., Helwani, F. M., Winkler, I. G., Nowlan, B., Barbier, V., Powell, R. J., Engler, G. A., Diakiw, S. M., Zannettino, A. C. W., Martin, S., Pattabiraman, D., D'Andrea, R. J., Lewis, I. D. and Levesque, J. P. (2015) 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. Leukemia, 29 10: 2075-2085. doi:10.1038/leu.2015.102


Author Forristal, C. E.
Brown, A. L.
Helwani, F. M.
Winkler, I. G.
Nowlan, B.
Barbier, V.
Powell, R. J.
Engler, G. A.
Diakiw, S. M.
Zannettino, A. C. W.
Martin, S.
Pattabiraman, D.
D'Andrea, R. J.
Lewis, I. D.
Levesque, J. P.
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
Journal name Leukemia   Check publisher's open access policy
ISSN 1476-5551
0887-6924
Publication date 2015-05-15
Sub-type Article (original research)
DOI 10.1038/leu.2015.102
Volume 29
Issue 10
Start page 2075
End page 2085
Total pages 11
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Collection year 2016
Language eng
Formatted 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.
Keyword Stem cell
Hematopoietic cell
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Mater Research Institute-UQ (MRI-UQ)
Official 2016 Collection
School of Medicine Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 5 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 6 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Tue, 09 Jun 2015, 10:26:11 EST by System User on behalf of Scholarly Communication and Digitisation Service