Mitoxantrone-liposome Sensitizes <i>FLT3-ITD</i> Acute Myeloid Leukemia to Gilteritinib Treatment

FMS-like tyrosine kinase 3 (<i>FLT3</i>) is the most frequently mutated gene in acute myeloid leukemia (AML), and is associated with poor prognosis and a high relapse rate. Gilteritinib, a second-generation FLT3 inhibitor, is an important target drug for treating patients with <i>FLT3</i>-internal tandem duplication (ITD) AML, is approved for the treatment of relapsed/refractory <i>FLT3</i>-mutant acute myeloid leukemia, although challenges such as drug resistance and reduced potency remain. Herein, mitoxantrone-liposomes sensitized <i>FLT3-ITD</i> AML cells to gitretinib both <i>in vivo</i> and <i>in vitro</i>. RNA-sequencing revealed that combination treatment resulted in specific changes in gene expression as well as predicted the mechanism. Primary AML cells harvested from patients with <i>FLT3-ITD</i> AML showed a significant response to combination treatment <i>in vitro.</i> Our data suggests a novel and promising therapeutic strategy for patients with <i>FLT3-ITD</i> AML and relapsed/refractory FTL3-ITD AML.