Xie Lichun, Xu Ye, Fan Chuiqin, Liao Maochuan, Zhou Guichi, Fen Chen, Ma Lian, Wen Fei-Qiu
Department of Obstetrics and Gynecology, Department of Paediatrics, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, Guangdong-Hong Kong-Macao Greater Bay Area Higher Education Joint Laboratory of Maternal-Fetal Medicine; The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, 510140, Guangdong, China.
Department of Haematology/Oncology, Shenzhen Children's Hospital, No. 7019 Yitian Rd, Shenzhen, Guangdong, China.
Sci Rep. 2025 Apr 24;15(1):13976. doi: 10.1038/s41598-025-97345-0.
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.
儿童费城染色体阳性（Ph）急性淋巴细胞白血病（ALL）的预后较差，很大程度上是由于诊断和监测治疗效果存在挑战。最近的研究表明，环状RNA（circRNA）是各种肿瘤潜在的诊断和预后生物标志物，以表明circRNA在识别或作为新的治疗靶点方面的潜在作用。在此，我们分析了3例Ph ALL患者诊断时（CK1组）、治疗后第19天（T1组）和首次完全缓解时（治疗后第46天，T2组）以及1例Ph ALL患者诊断时（CK2组）样本中的circRNA表达谱。在CK1组和CK2组之间共发现922个潜在与RNA降解、癌症中的微小RNA、丙酸代谢和泛素介导的蛋白水解相关的差异表达环状RNA（DECs）（626个上调，296个下调）。此外，我们在CK1组和T1组之间鉴定出224个DECs（129个上调，95个下调），在CK1组和T2组之间鉴定出225个DECs（136个上调，89个下调），其中136个表达上调，89个表达下调。hsa_circ_0012152和hsa_circ_0009024在Ph ALL患者中的水平显著升高，这些circRNA水平变化通过qRT-PCR得到证实，表明它们作为诊断生物标志物的潜力。大多数上调的DECs经历了N6-甲基腺苷（m6A）修饰，基于所鉴定的circRNA和DECs，现在对其特定作用有了更好的理解，理想情况下表明这些发现如何影响Ph ALL的诊断和治疗。本研究结果增加了我们对m6A修饰的circRNA在Ph ALL发病机制中作用的理解。
