Interferon Therapy in Acute Myeloid Leukemia: Biological Rationale, Clinical Evidence, and Future Directions

Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy characterized by uncontrolled clonal proliferation of immature myeloid blasts in bone marrow and peripheral blood. The contemporary therapeutic landscape for AML spans a broad spectrum of interventions, relying on cytotoxic chemotherapy, hypomethylating agents, and an expanding array of targeted therapies to accommodate both patients eligible for intensive induction and those requiring lower intensity regimens. Allogeneic hematopoietic stem cell transplantation is performed with curative intent in eligible high-risk patients, and donor lymphocyte infusion is utilized to prevent or treat post-transplant early relapse. Despite ongoing therapeutic advances, the overall prognosis for AML remains unsatisfactory with a five-year relative survival rate of approximately 31.9%. Driven by an evolving understanding of AML biology, particularly the roles of leukemic stem cells and measurable residual disease, interferon (IFN) therapy, specifically type I and type II IFNs, has emerged as a compelling therapeutic candidate, distinguished by its direct anti-leukemic effect and indirect anticancer activities, notably via immunomodulatory effects. This review outlines the biological rationale and clinical evidence for current IFN therapy in AML, aiming to inform future preclinical and clinical investigations.