Gene expression profile of a FLT3-ITD acute myeloid leukemia cell line treated with FLT3 inhibitors for six and twelve hours

Adaptive resistance is an important mechanism of resistance to tyrokine kinase inhibitors in cancer. With this study we aimed to determine which signaling pathways may contribute to adaptive resistance by examining the mRNA profiles of FLT3-ITD AML cells treated with the FLT3 inhibitor, AC220. We also aimed to determine whether our novel inhibitor, NCGC1481, would inhibit the activation of these pathways. We concluded that AC220 induces activation of innate immune signaling and NCGC1481 prevents this activation. Overall design: mRNA profiles of a FLT3-ITD AML cell line treated with AC220 or novel compound, NCGC1481, compared to DMSO control at 6 and 12 hours of treatment

适应性耐药（Adaptive Resistance）是癌症对酪氨酸激酶抑制剂产生耐药的重要机制。本研究通过分析经FLT3抑制剂（FLT3 inhibitor）AC220处理的FLT3内部串联重复急性髓系白血病（FLT3-ITD AML）细胞的mRNA表达谱，旨在明确哪些信号通路参与适应性耐药的发生；同时探究新型抑制剂NCGC1481能否抑制上述通路的激活。研究结论显示，AC220可诱导先天免疫信号通路激活，而NCGC1481可阻断这一激活过程。整体实验设计：在处理6小时与12小时两个时间点，分别采集经AC220及新型化合物NCGC1481处理的FLT3-ITD AML细胞系的mRNA表达谱，并与二甲基亚砜（Dimethyl sulfoxide, DMSO）对照组进行比较。