Combined FLT3 and EZH1/2 inhibition reduced leukemia stem cells and improved myeloid differentiation in AML, suggesting a novel therapeutic approach.
Key Points
To evaluate the combined effectiveness of FLT3 and EZH1/2 inhibitors in reducing leukemia stem cells and promoting myeloid differentiation in acute myeloid leukemia.
Utilized patient-derived xenograft (PDX) models of FLT3-ITD AML for treatment assessment.
Administered gilteritinib and valemetostat to models and analyzed leukemia burden and differentiation.
Conducted serial bone marrow assessments and single cell RNA-Seq analysis to monitor treatment effects.
Combination treatment significantly reduced leukemia stem cells (LSCs) in bone marrow and spleen.
Increased myeloid differentiation observed post-treatment, primarily noted in neutrophils and monocytes.
Single cell RNA-Seq analysis revealed distinct differentiation states between gilteritinib alone and combination treatments.