Figure 3.
Dexamethasone synergizes with quizartinib in FLT3-ITD AML by reversing the inflammatory gene signature. (A) Three-dimensional graph showing the synergy score of quizartinib and dexamethasone combination in MV4-11 cells (48 hours). ZIP, 0 interaction potency. (B) IncuCyte live tracking of activated caspase-3/7 (total green fluorescence) in MV4-11 cells treated with quizartinib (100 nM) and dexamethasone (50 µM) alone or in combination. (C) Combined analysis of replicate experiments to quantify live cells (Annexin V and 7-AAD negative) using FACS analysis for the indicated time points and drug treatments (10 nM quizartinib and 100 nM dexamethasone) in MV4-11 cells. (D) A heat map of differentially expressed genes (green, downregulated; red, upregulated) in MV4-11 cells treated for 48 hours with the indicated drugs (10 nM quizartinib and 100 nM dexamethasone). Pathway analysis shows genes upregulated in quizartinib-treated cells and downregulated in cells treated with the combination of quizartinib and dexamethasone (i). RNA sequencing was conducted in 3 biological replicates. MHC, major histocompatibility complex.

Dexamethasone synergizes with quizartinib in FLT3-ITD AML by reversing the inflammatory gene signature. (A) Three-dimensional graph showing the synergy score of quizartinib and dexamethasone combination in MV4-11 cells (48 hours). ZIP, 0 interaction potency. (B) IncuCyte live tracking of activated caspase-3/7 (total green fluorescence) in MV4-11 cells treated with quizartinib (100 nM) and dexamethasone (50 µM) alone or in combination. (C) Combined analysis of replicate experiments to quantify live cells (Annexin V and 7-AAD negative) using FACS analysis for the indicated time points and drug treatments (10 nM quizartinib and 100 nM dexamethasone) in MV4-11 cells. (D) A heat map of differentially expressed genes (green, downregulated; red, upregulated) in MV4-11 cells treated for 48 hours with the indicated drugs (10 nM quizartinib and 100 nM dexamethasone). Pathway analysis shows genes upregulated in quizartinib-treated cells and downregulated in cells treated with the combination of quizartinib and dexamethasone (i). RNA sequencing was conducted in 3 biological replicates. MHC, major histocompatibility complex.

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