Inhibition of the proteasome and proteaphagy enhances apoptosis in FLT3‐ITD‐driven acute myeloid leukemia

摘要

Autophagy (Atg) regulates cytotoxicity after proteasome inhibition in acute myeloid leukaemia (AML) cells expressing fms‐like tyrosine kinase 3 (FLT3) mutations. Here, we show that the proteasome inhibitor bortezomib activates proteaphagy in AML cells expressing FLT3‐internal tandem duplication (ITD), but not in cells with wild‐type FLT3. Chemical inhibition of Atg blocking autophagosome‐lysosome fusion or the Atg receptor p62 efficiently inhibits proteaphagy and enhances bortezomib‐induced apoptosis in FLT3‐ITD‐driven leukemic cells.