Acute myeloid leukemia (AML) is an aggressive blood cancer characterized by the accumulation of immature myeloid cells. Current treatments often fail to achieve durable remission, underscoring the need for innovative therapeutic approaches. CD97 is a cell surface protein with broad, increased expression on AML cells compared to normal blood stem and progenitor cells. Moreover, CD97 overexpression in AML patients has been associated with poor survival, thus emerging as a potential therapeutic target.