Figure 5. AMPK is a source of resistance to CPI-613.
(A) Western blot analysis of patient samples taken on cycle 1 day 1 at the indicated time points before and following infusion of CPI-613 for phosphorylation of AMPK. OCI lanes refer to the positive control, OCI-AML3 cells treated with CPI-613 for the indicated time. Actin was used as a loading control. (B) Competition assay. MFL2 cells expressing Cas9 were partially infected with GFP labeled vector that expressed an sgRNA targeting AMPK in conjunction with a GFP reporter. The mixed population was treated with the indicated therapy for 72 hours and the percentage of GFP+ cells was assessed and normalized to controls. (C) Western blot analysis of control or AMPK-deleted cells. Actin was used as a loading control. (D) Viability assays. Control or AMPK deleted cells were incubated with the indicated therapy for 72 hours in viability was assessed.