Figure 2.
Anti-inflammatory drugs enhance the cytotoxicity of FLT3 inhibitors in FLT3-mutant AML cells. (A) Analysis scheme used to identify druggable targets in DTPs. (B) Drug screening of DTPs and parental MV4-11 cells using a library of 1500 FDA-approved drugs. Cells were incubated with the drug library for 48 hours, and viability was measured using CellTiter-Glo. The top 50 drugs that selectively kill DTPs or parental cells are highlighted by red boxes. Pie chart shows the top 50 drugs that selectively kill DTPs (i) or parental cells (ii). (C) Representative images (n = 4) of FACS analysis of APC-Annexin-V and 7-AAD stained MV4-11 cells following treatment with quizartinib (100 nM) alone or in combination with 50 µM dexamethasone (Dex), prednisolone (Pred), or triamcinolone (Triam) for 48 hours. (D-E) Combined analysis of replicate experiments to quantify dead cells (Annexin-V positive) using APC-Annexin-V and 7-AAD staining and FACS analysis for the indicated drug combinations (100 nM FLT3 inhibitors, 1 µM cytarabine, and 50 µM GCs) in MV4-11 (D) and THP1 (E) cells. WT, wild-type.

Anti-inflammatory drugs enhance the cytotoxicity of FLT3 inhibitors in FLT3-mutant AML cells. (A) Analysis scheme used to identify druggable targets in DTPs. (B) Drug screening of DTPs and parental MV4-11 cells using a library of 1500 FDA-approved drugs. Cells were incubated with the drug library for 48 hours, and viability was measured using CellTiter-Glo. The top 50 drugs that selectively kill DTPs or parental cells are highlighted by red boxes. Pie chart shows the top 50 drugs that selectively kill DTPs (i) or parental cells (ii). (C) Representative images (n = 4) of FACS analysis of APC-Annexin-V and 7-AAD stained MV4-11 cells following treatment with quizartinib (100 nM) alone or in combination with 50 µM dexamethasone (Dex), prednisolone (Pred), or triamcinolone (Triam) for 48 hours. (D-E) Combined analysis of replicate experiments to quantify dead cells (Annexin-V positive) using APC-Annexin-V and 7-AAD staining and FACS analysis for the indicated drug combinations (100 nM FLT3 inhibitors, 1 µM cytarabine, and 50 µM GCs) in MV4-11 (D) and THP1 (E) cells. WT, wild-type.

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