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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.
Brown, A.
Helwani, F.
Winkler, I.
Nowlan, B.
Barbier, V.
Powell, R.
Engler, G.
Diakiw, S.
Zannettino, A.
Martin, S.
Pattabiraman, D.
D'Andrea, R.
Lewis, I.
Levesque, J.
Citation: Leukemia, 2015; 29(10):2075-2085
Publisher: Nature Publishing Group
Issue Date: 2015
ISSN: 0887-6924
Statement of
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
RMID: 0030028737
DOI: 10.1038/leu.2015.102
Grant ID:
Appears in Collections:Medicine publications

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