| First Author | Forristal CE | Year | 2015 |
| Journal | Leukemia | Volume | 29 |
| Issue | 10 | Pages | 2075-85 |
| PubMed ID | 25921247 | Mgi Jnum | J:225618 |
| Mgi Id | MGI:5693711 | Doi | 10.1038/leu.2015.102 |
| Citation | Forristal CE, et al. (2015) 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. Leukemia 29(10):2075-85 |
| abstractText | Hypoxia-inducible factor (HIF)-1alpha accumulation promotes hematopoietic stem cells' quiescence and is necessary to maintain their self-renewal. However, the role of HIF-2alpha in hematopoietic cells is less clear. We investigated the role of HIF-2alpha in leukemia and lymphoma cells. HIF-2alpha 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-2alpha, we transduced human HIF-2alpha cDNA in mouse syngeneic models of myeloid preleukemia and a transgenic model of B lymphoma. Ectopic expression of HIF-2alpha accelerated leukemia cell proliferation in vitro. Mice transplanted with cells transduced with HIF-2alpha died significantly faster of leukemia or B lymphoma than control mice transplanted with empty vector-transduced cells. Conversely, HIF-2alpha 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-2alpha 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-2alpha expression had a trend to higher disease-free survival in univariate analysis. The different effects of HIF-2alpha overexpression in mouse models of leukemia and human AML illustrates the complexity of this mutliclonal disease. |
