biostudies-literatureUnknown47(10)Fujii-Hanamoto A<b>Background</b>: FLT3 mutations, including internal tandem duplication (ITD) and tyrosine kinase domain (TKD) point mutations, represent common genetic alterations in acute myeloid leukemia (AML), with FLT3-ITD associated with poor prognosis. Although FLT3 tyrosine kinase inhibitors (TKIs), such as quizartinib (Quiz) and gilteritinib, have improved clinical outcomes, secondary TKD mutations, particularly the gatekeeper mutation F691L, confer significant resistance. We previously demonstrated that chlorpromazine (CPZ), an antipsychotic drug, inhibits clathrin-mediated endocytosis and selectively suppresses the growth of cancer cells harboring mutant receptor tyrosine kinases. <b>Methods</b>: In this study, we examined the efficacy of CPZ in overcoming TKI resistance using Ba/F3 cells exprCurrent issues in molecular biology797https://www.ebi.ac.uk/biostudies/studies/S-EPMC12564577biostudies-literatureAntipsychotic Chlorpromazine Suppresses STAT5 Signaling, Overcomes Resistance Mediated by the Gatekeeper Mutation FLT3-ITD/F691L, and Synergizes with Quizartinib in FLT3-ITD-Positive Cells.PMC12564577Tanaka HSerizawa KMatsumura IHanamoto HFujii-Hanamoto AHaeno TFujiwara RMiyake YMorita YRai SKumode TFujimoto KfalseAntipsychotic Chlorpromazine Suppresses STAT5 Signaling, Overcomes Resistance Mediated by the Gatekeeper Mutation FLT3-ITD/F691L, and Synergizes with Quizartinib in FLT3-ITD-Positive Cells.<b>Background</b>: FLT3 mutations, including internal tandem duplication (ITD) and tyrosine kinase domain (TKD) point mutations, represent common genetic alterations in acute myeloid leukemia (AML), with FLT3-ITD associated with poor prognosis. Although FLT3 tyrosine kinase inhibitors (TKIs), such as quizartinib (Quiz) and gilteritinib, have improved clinical outcomes, secondary TKD mutations, particularly the gatekeeper mutation F691L, confer significant resistance. We previously demonstrated that chlorpromazine (CPZ), an antipsychotic drug, inhibits clathrin-mediated endocytosis and selectively suppresses the growth of cancer cells harboring mutant receptor tyrosine kinases. <b>Methods</b>: In this study, we examined the efficacy of CPZ in overcoming TKI resistance using Ba/F3 cells expr2025-01-01T00:00:00Z2025 Sep2026-05-14T03:18:38.034Z2026-05-14T03:12:13.046ZS-EPMC125645774115074510.3390/cimb47100797