Monoclonal antibodies targeting specific cell surface antigens have emerged as a promising therapeutic approach for acute myeloid leukemia (AML), thus widening the treatment landscape of this heinous disease. These antibodies have been designed to selectively target and eliminate leukemic cells while limiting damage to the normal hematopoietic counterpart. Among the potential targets on AML cells, CD33, CD123, and CD47 have shown the major potential in preclinical and clinical trials. Additionally, conjugation of monoclonal antibodies with cytotoxic agents has further enhanced their therapeutic efficacy. Nonetheless, challenges such as antigen heterogeneity, resistance mechanisms, and the immunosuppressive tumor microenvironment remain significant barriers to achieving durable remission in AML patients. This review explores the mechanisms of action, current clinical developments, and ongoing trials into the role of monoclonal antibodies in AML, highlighting their potential to improve clinical outcomes when used alone or in combination with conventional therapies, making them thus able to become, in the near future, a cornerstone in the treatment of AML.
