| First Author | Zhang H | Year | 2012 |
| Journal | Blood | Volume | 119 |
| Issue | 11 | Pages | 2595-607 |
| PubMed ID | 22275380 | Mgi Jnum | J:182536 |
| Mgi Id | MGI:5315812 | Doi | 10.1182/blood-2011-10-387381 |
| Citation | Zhang H, et al. (2012) HIF1alpha is required for survival maintenance of chronic myeloid leukemia stem cells. Blood 119(11):2595-607 |
| abstractText | Hypoxia-inducible factor-1alpha (HIF1alpha), a master transcriptional regulator of the cellular and systemic hypoxia response, is essential for the maintenance of self-renewal capacity of normal HSCs. It is still unknown whether HIF1alpha has a role in survival regulation of leukemia stem cells (LSCs) in chronic myeloid leukemia (CML). Using a mouse model of CML, here we report that HIF1alpha plays a crucial role in survival maintenance of LSCs. Deletion of HIF1alpha impairs the propagation of CML through impairing cell-cycle progression and inducing apoptosis of LSCs. Deletion of HIF1alpha results in elevated expression of p16(Ink4a) and p19(Arf) in LSCs, and knockdown of p16(Ink4a) and p19(Arf) rescues the defective colony-forming ability of HIF1alpha(-/-) LSCs. Compared with normal HSCs, LSCs appear to be more dependent on the HIF1alpha pathway. Together, these results demonstrate that HIF1alpha represents a critical pathway in LSCs and inhibition of the HIF1alpha pathway provides a therapeutic strategy for eradicating LSCs in CML. |
