Glucocorticoids enhance the anti-leukemic activity of FLT3 inhibitors in FLT3 mutant acute myeloid leukemia

Utilizing genome wide transcriptome analysis and drug screen we demonstrate that upregulation of inflammatory pathways is a key mechanism of drug tolerance to FLT3 targeted inhibitors in AML Overall design: Performed RNA-seq after isolating cells that survive treatment with DMSO or quizartinib for 48h or after recovery in drug free media for 13 or 30 days. Another set of RNA-seq was performed using cells that survive treatment with DMSO, dexamethasone, quizartinib or the combination of quizartinib and dexamethasone for 48h or 5 days(in the case of combination tretment for 5days quizartinib was kept for 5 days but dexemethasone was added on Day 3).