Ferroptosis in Treatment of Drug-Resistant Leukemia

The major difficulty in leukemia treatment is drug resistance. Novel therapeutic approaches are being investigated to improve treatment efficiency. One of the research interests is the induction of ferroptosis, that bypasses many potential mutation sites in leukemic cells that spared them from apoptosis. Recent studies suggested that AML exhibits positive correlation with Nrf2 activity which triggers improved antioxidative defense mechanism of the cell, inhibiting this pathway enhances cellular ferroptosis sensitivity. In ALL, mutated FSP1 is silenced, leaving GPX4 pathway the sole antioxidation defense mechanism, which makes ferroptosis more inducible when such pathway is targeted. In CML, FRGs are being downregulated. However, the drug-resistant subtype of CML appeared to be more vulnerable to ferroptosis. In this review, the experiments evidence is discussed across these three subtypes. Several compounds are highlighted which have the capability of inducing ferroptosis and the effect of co-administration with existing therapeutic drugs is demonstrated that shows further enhancement in ferroptosis.