Chronic myeloid leukemia (CML) is a rare clonal myeloproliferative malignancy, which is caused by a reciprocal translocation between chromosomes 9 and 22 t (9; 22)(q34; q11). Altered circle RNAs (circRNAs) could contribute to leukemogenesis. In this study, we aimed to investigate the expression profiling of circRNAs in CML. We performed circRNA-sequencing to identify differentially expressed circRNAs in CML cells. Furthermore, we found that circ_100053 was significantly upregulated in peripheral blood mononuclear cells (PBMC) and serum samples from CML compared with healthy controls. CircRNA_100053 expression was associated with clinical stage (p= 0.037) and BCR/ABL mutant status (p= 0.008). High circ_100053 expression predicted a poor outcome of CML patients and imatinib resistance, suggesting the putative role of circ_100053 as an CML biomarker. Our findings provide insights on circRNAs expression in the development and treatment of CML.