Mitoxantrone-liposome sensitizes Flt3-ITD acute myeloid leukemia to gilteritinib treatment

FMS-like tyrosine kinase 3 (FLT3) is the most frequently mutated gene in acute myeloid leukemia (AML), and is associated with a poor prognosis and high relapse rate. Gilteritinib, as a second-generation FLT3 inhibitor, is an important target drug in the treatment of FLT3-ITD AML patients, but it still faces the problems of drug resistance and reduced potency. In this study, we found that mitoxantrone-liposome can sensensitized gilteritinib and enhanced the therapeutic effect in vivo and in vitro. RNA-sequencing revealed that the combination treatment resulted in specific changes in gene expression, reduced drug resistance and the mechanism. Primary AML cells harvested from patients with FLT3-ITD AML showed a significant response to combination treatment in vitro. Our data suggest represents a novel and promising therapeutic strategy for FLT3-ITD AML patients and relapsed/refractory(R/R) AML. Overall design: MV4-11 cell lines were cultured with DMSO, Mitoxantrone (20 nM), or Gilteritinib(25 nM) , or combination(Mitoxantrone 20 nM plus Gilteritinib 20 nM) for 24 h, followed by RNA-seq