Dysregulated ClpP Activation Depletes AML Cells and Restores T-cell Function via Metabolic Competition

We employed single-cell RNA sequencing (scRNA-seq) to investigate immune responses in a syngeneic acute myeloid leukemia (AML) model generated by transplantation of murine WEHI-3-luc cells into BALB/c mice. Treatment with the novel CLPP inhibitor IMP125 (5 mg/kg) demonstrated superior therapeutic effects compared with ONC201, lower-dose IMP125, and conventional chemotherapy agents, including reductions in leukemic burden, prolonged survival, and enhanced immune activation. Spleen, bone marrow, and liver tissues were profiled to provide insights into the immune mechanisms underlying IMP125 efficacy.