| First Author | Velasco-Hernandez T | Year | 2014 |
| Journal | Blood | Volume | 124 |
| Issue | 24 | Pages | 3597-607 |
| PubMed ID | 25267197 | Mgi Jnum | J:220797 |
| Mgi Id | MGI:5636142 | Doi | 10.1182/blood-2014-04-567065 |
| Citation | Velasco-Hernandez T, et al. (2014) HIF-1alpha can act as a tumor suppressor gene in murine acute myeloid leukemia. Blood 124(24):3597-607 |
| abstractText | Self-renewal of hematopoietic stem cells (HSCs) and leukemia-initiating cells (LICs) has been proposed to be influenced by low oxygen tension (hypoxia). This signaling, related to the cellular localization inside the bone marrow niche and/or influenced by extrinsic factors, promotes the stabilization of hypoxia-inducible factors (HIFs). Whether HIF-1alpha can be used as a therapeutic target in the treatment of myeloid malignancies remains unknown. We have used 3 different murine models to investigate the role of HIF-1alpha in acute myeloid leukemia (AML) initiation/progression and self-renewal of LICs. Unexpectedly, we failed to observe a delay or prevention of disease development from hematopoietic cells lacking Hif-1alpha. In contrast, deletion of Hif-1alpha resulted in faster development of the disease and an enhanced leukemia phenotype in some of the investigated models. Our results therefore warrant reconsideration of the role of HIF-1alpha and, as a consequence, question its generic therapeutic usefulness in AML. |
