Delineating resistance mechanisms to gilteritinib combination therapy in AML: shifts in cell state, signaling and mutations

Acute myeloid leukemia (AML) is a malignancy with a poor survival rate, primarily due to resistance to chemotherapy.Combination therapy using gilteritinib with venetoclax, has been explored as a novel strategy to overcome resistance mechanisms. Gilteritinib plus venetoclax combination therapy, especially in the context of F691L mutations, maintains a primitive cell state characterized by increased LSPCs, GMP, and GMP-like cells in both in vitro and patient samples.