Hif-1α Deletion May Lead to Adverse Treatment Effect in a Mouse Model of MLL-AF9-Driven AML.

ABSTRACT: Relapse of acute myeloid leukemia (AML) remains a significant clinical challenge due to limited therapeutic options and poor prognosis. Leukemic stem cells (LSCs) are the cellular units responsible for relapse in AML, and strategies that target LSCs are thus critical. One proposed potential strategy to this end is to break the quiescent state of LSCs, thereby sensitizing LSCs to conventional cytostatics. The hypoxia-inducible factor (HIF) pathway is a main driver of cellular quiescence and a potential therapeutic target, with precedence from both solid cancers and leukemias. Here, we used a conditional knockout Hif-1α mouse model together with a standard chemotherapy regimen to evaluate LSC targeting in AML. Contrary to expectation, our studies revealed that Hif-1α-deleted-leukemias displa

SUBMITTER: Velasco-Hernandez T 

PROVIDER: S-EPMC6335588 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature