FLT3L-based drug conjugate effectively targets chemoresistant leukemia stem cells in acute myeloid leukemia.

ABSTRACT: Acute myeloid leukemia (AML) is a heterogeneous malignancy with poor prognosis due to relapse and chemotherapy resistance. FLT3 mutations promote AML and predict adverse outcomes. As most AML cells express FLT3, it represents a promising therapeutic target. In this study, we develop FL-Fc-DM1, a FLT3-targeted conjugate linking FLT3 ligand-Fc to DM1. FL-Fc-DM1 demonstrates potent anti-leukemic activity in vitro, ex vivo, and in both cell line- and patient-derived xenograft models. Notably, it effectively targets cytarabine-resistant AML cells by promoting cell cycle entry and inducing apoptosis. FL-Fc-DM1 also significantly reduces functional leukemia stem cell frequency, as demonstrated by limiting dilution transplantation assays. The therapeutic efficacy can be further strengthened by BH3

SUBMITTER: Zhang D 

PROVIDER: S-EPMC12629795 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature