AML is a complex disease caused by multiple molecular mechanisms. As an important regulatory molecule, the role of circRNA in AML is not fully understood. By performing high-throughput sequencing on clinical samples, we systematically identified the differences in circRNA expression and distribution between AML and healthy donor samples. One circular RNA, circAFF2, was found to be significantly upregulated in AML patients. Functional studies showed that knockdown of circAFF2 could significantly inhibit the proliferation of AML cells and promote their apoptosis. Overexpression of circAFF2 can have opposite effects. In vivo experiments showed that transplantation of AML cells with circAFF2 knockdown slowed the proliferation and infiltration and prolonged the survival time of mice compared to controls. Further studies showed that circAFF2 can promote the degradation of PML mRNA by binding to the 3'UTR of PML mRNA, thereby affecting the proliferation and apoptosis of AML cells. In conclusion, our work demonstrates that circAFF2 can bind to PML mRNA to regulate AML cell function, providing new insights into the mechanism of AML development and potential targets for clinical diagnosis and treatment.