Oncogenic KIT mutations induce STAT3-dependent autophagy to support cell proliferation in acute myeloid leukemia.

ABSTRACT: Autophagy is associated with both survival and cell death in myeloid malignancies. Therefore, deciphering its role in different genetically defined subtypes of acute myeloid leukemia (AML) is critical. Activating mutations of the KIT receptor tyrosine kinase are frequently detected in core-binding factor AML and are associated with a greater risk of relapse. Herein, we report that basal autophagy was significantly increased by the KIT^D816V mutation in AML cells and contributed to support their cell proliferation and survival. Invalidation of the key autophagy protein Atg12 strongly reduced tumor burden and improved survival of immunocompromised NSG mice engrafted with KIT^D816V TF-1 cells. Downstream of KIT^D816V, STAT3, but not AKT or ERK pathways, was ident

SUBMITTER: Larrue C 

PROVIDER: S-EPMC6635375 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature