| First Author | Velasco-Hernandez T | Year | 2015 |
| Journal | Leukemia | Volume | 29 |
| Issue | 12 | Pages | 2366-74 |
| PubMed ID | 26104662 | Mgi Jnum | J:227310 |
| Mgi Id | MGI:5700139 | Doi | 10.1038/leu.2015.156 |
| Citation | Velasco-Hernandez T, et al. (2015) Loss of HIF-1alpha accelerates murine FLT-3(ITD)-induced myeloproliferative neoplasia. Leukemia 29(12):2366-74 |
| abstractText | Hypoxia-induced signaling is important for normal and malignant hematopoiesis. The transcription factor hypoxia-inducible factor-1alpha (HIF-1alpha) has a crucial role in quiescence and self-renewal of hematopoietic stem cells (HSCs), as well as leukemia-initiating cells (LICs) of acute myeloid leukemia and chronic myeloid leukemia. We have investigated the effect of HIF-1alpha loss on the phenotype and biology of FLT-3(ITD)-induced myeloproliferative neoplasm (MPN). Using transgenic mouse models, we show that deletion of HIF-1alpha leads to an enhanced MPN phenotype reflected by an increased number of white blood cells, more severe splenomegaly and decreased survival. The proliferative effect of HIF-1alpha loss is cell intrinsic as shown by transplantation into recipient mice. HSC loss and organ-specific changes in the number and percentage of long-term HSCs were the most pronounced effects on a cellular level after HIF-1alpha deletion. Furthermore, we found a metabolic hyperactivation of malignant cells in the spleen upon loss of HIF-1alpha. Some of our findings are in contrary to what has been previously described for the role of HIF-1alpha in other myeloid hematologic malignancies and question the potential of HIF-1alpha as a therapeutic target. |
