Date of Award
Master of Science (MS)
The TANK-binding kinase 1 (TBK1) is a cytoplasmic, serine/threonine kinase and a critical activator of the innate immune system. Reports have implicated TBK1 as a promoter of multiple cancer types. Acute myeloid leukemia (AML) is a cancer arising from the hematopoietic stem/progenitor cells (HSPCs). Although ~70% of AML patients achieve complete remission with chemotherapy, at least half will relapse due to the failure to eradicate leukemia stem cells (LSCs). As our previous data indicate the TLR-TAK1/TICAM-1 axes regulate LSCs, we suspect TBK1 also regulates LSCs. To study TBK1 in AML, we generated tamoxifen-inducible, Tbk1-knockout (Tbk1NULL) mice and Tbk1NULL MLL-AF9+ mouse HSPCs. We found that Tbk1 deletion ablates the c-Kit+Flt3+ subset of MLL-AF9+ HSPCs without perturbing homeostatic hematopoiesis; the loss of Tbk1 also increases the expression of c-Fms/CD115 on MLL-AF9+ HSPCs. Our study suggests that TBK1 blockade can selectively and effectively target FLT3+ LSCs in AML treatment.
Runde, Austin Patrick, "Murine TBK1 Is Required by Flt3+ Leukemia Stem Cells Yet Dispensable in Homeostatic Hematopoiesis" (2023). Master's Theses. 4485.
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.
Copyright © 2023 Austin Patrick Runde