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. Author manuscript; available in PMC: 2020 May 15.
Published in final edited form as: Clin Cancer Res. 2019 Jul 18;25(22):6815–6826. doi: 10.1158/1078-0432.CCR-19-0832

Figure 2. Combination of midostaurin and venetoclax mitigates venetoclax-induced upregulation of p-ERK and prevents rebound of p-ERK during midostaurin treatment.

Figure 2.

(A-C) FLT3-ITD AML cell lines MOLM-13, MV4–11, and primary patient sample AML#171 were treated with midostaurin alone or in combination with venetoclax for up to 24 hours. Representative Western blots generated using whole cell lysates are shown. Densitometry measurements, shown below the corresponding blot, were normalized to β-actin and expressed as fold change compared to vehicle control. (D) MOLM-13 and MV4–11 cell lines were treated for 4–24 hours with vehicle control, midostaurin, venetoclax, or in combination. Annexin V-FITC/PI staining and flow cytometry results are shown. ***indicates p<0.001. (E) MOLM-13, MV4–11, and primary patient sample AML#180 were treated with variable concentrations of venetoclax. Representative Western blots are shown. Densitometry measurements, shown below the corresponding blot, were normalized to β-actin and expressed as fold change compared to vehicle control. (F-G) AML cells were treated with venetoclax alone or in combination with the ERK- selective inhibitor SCH772984 for 24 hours. Flow cytometry and Western blot analyses are shown. ***indicates p<0.001. Densitometry measurements, shown below the corresponding blot, were normalized to β-actin and expressed as fold change compared to vehicle control. (H-I) AML cells were treated with midostaurin alone or in combination with the ERK selective inhibitor SCH772984 for 24 hours. Flow cytometry and Western blot analyses are shown. ***indicates p<0.001. Densitometry measurements, shown below the corresponding blot, were normalized to β-actin and expressed as fold change compared to vehicle control.