Differential expression and functional analysis of circular RNAs and m6A modifications in children with Philadelphia...

Philadelphia chromosome-positive (Ph⁺) acute lymphoblastic leukaemia (ALL) in childhood is associated with dismal outcomes, in large part due to challenges in diagnosis and monitoring therapeutic efficacy. Recent studies suggest that circular RNAs (circRNAs) are potential diagnostic and prognostic biomarkers for various tumours. to indicate the potential role of circRNAs in identifying or serving as novel targets for treatments. Here, we analysed CircRNA expression profiles in samples from three Ph⁺ ALL patients at diagnosis (CK1 group), on day 19 after treatment (T1 group) and in first complete remission (day 46 after treatment, T2 group), as well as one Ph^- ALL patient at diagnosis (CK2 group). A total of 922 differentially expressed circRNAs (DECs) potentially associated with RNA degradation, microRNAs in cancer, propanoate metabolism and ubiquitin-mediated proteolysis were found (626 upregulated and 296 downregulated) between the CK1 and CK2 groups. In addition, we identified 224 DECs (129 upregulated and 95 downregulated) between the CK1 and T1 groups and 225 DECs (136 upregulated and 89 downregulated) between the CK1 and T2 groups, including 136 for which their expression was upregulated and 89 for which their expression was downregulated. The levels of hsa_circ_0012152 and hsa_circ_0009024 were significantly increased in Ph⁺ ALL patients, the changes in the levels of these circRNAs were confirmed by qRT‒PCR, indicating their potential as diagnostic biomarkers. Most upregulated DECs underwent N6-methyladenosine (m6A) modification noting the specific roles that are now better understood based on the circRNAs and DECs identified, and ideally suggesting how the findings could impact the diagnosis and treatment of Ph⁺ ALL The findings of this study increase our understanding of the roles of m6A-modified circRNAs in the pathogenesis of Ph⁺ ALL.