| First Author | Xiu Y | Year | 2018 |
| Journal | Cell Rep | Volume | 22 |
| Issue | 2 | Pages | 350-358 |
| PubMed ID | 29320732 | Mgi Jnum | J:270799 |
| Mgi Id | MGI:6278736 | Doi | 10.1016/j.celrep.2017.12.055 |
| Citation | Xiu Y, et al. (2018) Stabilization of NF-kappaB-Inducing Kinase Suppresses MLL-AF9-Induced Acute Myeloid Leukemia. Cell Rep 22(2):350-358 |
| abstractText | Canonical NF-kappaB signaling is constitutively activated in acute myeloid leukemia (AML) stem cells and is required for maintenance of the self-renewal of leukemia stem cells (LSCs). However, any potential role for NF-kappaB non-canonical signaling in AML has been largely overlooked. Here, we report that stabilization of NF-kappaB-inducing kinase (NIK) suppresses AML. Mechanistically, stabilization of NIK activates NF-kappaB non-canonical signaling and represses NF-kappaB canonical signaling. In addition, stabilization of NIK-induced activation of NF-kappaB non-canonical signaling upregulates Dnmt3a and downregulates Mef2c, which suppresses and promotes AML development, respectively. Importantly, by querying the connectivity MAP using up- and downregulated genes that are present exclusively in NIK-stabilized LSCs, we discovered that verteporfin has anti-AML effects, suggesting that repurposing verteporfin to target myeloid leukemia is worth testing clinically. Our data provide a scientific rationale for developing small molecules to stabilize NIK specifically in myeloid leukemias as an attractive therapeutic option. |
