Acute monocytic leukemia (AML-M5) is a rapidly progressing hematological malignancy characterized by limited therapeutic options and poor survival outcomes. Conventional therapies, such as intensive chemotherapy offer limited efficacy due to their lack of tumor specificity, significant systemic toxicities, and high risk of disease relapse after initial treatment, underscoring the need for more targeted therapeutic approaches. CD64 (FcγRI) is highly expressed on monocyte-derived myeloid leukemia cells and has been identified as a promising therapeutic target for the treatment of AML-M5. We have previously demonstrated that recombinant immunotoxins and their humanized counterparts (human cytolytic fusion proteins) can selectively target and eliminate CD64