Acute myeloid leukemia (AML) is a heterogeneous clonal disease of hematopoietic progenitor cells and the most common malignant myeloid disease in adults. Although significant progress has been made in treatment, the outlook remains bleak, and new therapeutic targets need to be sought. AP-2 complex subunit mu (AP2M1) is a core component of the clathrin-mediated endocytic machinery, AP2M1 plays a critical role in cancer progression. However, its function in acute myeloid leukemia (AML) progression remains unclear. Our study reveals that AP2M1 is highly expressed in AML and is associated with poor prognosis. Mechanistic studies suggest that this effect may result through cell cycle arrest and is associated with the tumor microenvironment, and our findings suggest that AP2M1 is a potential oncogene and prognostic marker for AML.