[Dobutamine Enhances the Targeted Inhibitory Effect of Quizartinib on FLT3-ITD Mutant Acute Myeloid Leukemia].

ABSTRACT

OBJECTIVE: To observe the inhibitory effect of dobutamine on proliferation of FLT3-ITD mutated acute myeloid leukemia (AML) cells and explore the feasibility of dobutamine as a monotherapy or in combination with quizartinib for the treatment of this type of AML. METHODS: FLT3-ITD mutant cell lines MOLM13 and MV4-11 were cultured in vitro and divided into control group, dobutamine treatment group, quizartinib treatment group, and dobutamine combined with quizartinib treatment group. Cell viability, ROS levels, and apoptosis rate were detected by CCK-8, Flow cytometry, respectively, as well as the expression of YAP1 protein by Western blot. RESULTS: Both dobutamine and quizartinib inhibited the proliferation of FLT3-ITD mutant AML cell lines. Compared with the control group, the dobutamine group exhibited a significant increase in ROS levels (P < 0.01), an increase in apoptosis rates (P < 0.05), and a decrease in YAP1 protein expression (P < 0.01), and decreased YAP1 expression (P < 0.05). CONCLUSION: Dobutamine as a monotherapy can inhibit theproliferation of FLT3-ITD mutated AML cells, inducing apoptosis. Additionally, the combination of quizartinib enhances the targeted inhibitory effect on FLT3-ITD mutated AML. The mechanism may involve the inhibition of YAP1 protein expression in AML cells of this type, leading to an increase in ROS levels and exerting its anti-tumor effects.