Arun Bhavyadharshini, John Geofrey, Raman Rajeshkumar
Hasan Lab, Department of Medical Oncology, Advanced Centre for Treatment Research and Education in Cancer, Tata Memorial Centre, Navi Mumbai, Maharashtra, India.
Homi Bhabha National Institute, Mumbai, Maharashtra, India.
J Hematol. 2025 Apr;14(2):43-55. doi: 10.14740/jh1384. Epub 2025 Apr 25.
Juvenile myelomonocytic leukemia (JMML) is an aggressive pediatric myelodysplastic/myeloproliferative neoplasm characterized by RAS pathway mutations and significant heterogeneity. Minimal residual disease (MRD) monitoring is crucial for evaluating treatment response and predicting relapse risk. MicroRNA (miRNAs), small non-coding RNAs with pivotal roles in gene regulation, have emerged as promising biomarkers for JMML MRD detection. This review explores the mechanistic role of miRNAs in JMML pathogenesis, emphasizing their diagnostic, prognostic, and therapeutic potential. Dysregulated miRNA profiles correlate with distinct JMML subgroups and disease progression, suggesting utility in non-invasive MRD monitoring. Emerging evidence highlights miR-150-5p as a tumor suppressor targeting STAT5b and its therapeutic potential in ameliorating JMML's aberrant signaling pathways. We compare traditional MRD methods, such as flow cytometry and polymerase chain reaction (PCR), with miRNA-based techniques, underscoring the latter's superior sensitivity, specificity, and non-invasiveness. Recent advances in miRNA profiling technologies, including next-generation sequencing and digital PCR, enable precise detection of residual leukemic cells and support personalized treatment approaches. Despite significant progress, challenges persist in standardizing miRNA-based assays and validating their clinical utility. Ethical considerations, including patient privacy and informed consent, remain critical for integrating miRNA diagnostics into routine care. This review provides a comprehensive synthesis of current knowledge on miRNA signatures in JMML, illuminating their transformative potential in MRD monitoring and paving the way for innovative therapeutic strategies.
青少年骨髓单核细胞白血病（JMML）是一种侵袭性儿童骨髓增生异常/骨髓增殖性肿瘤，其特征为RAS通路突变和显著的异质性。微小残留病（MRD）监测对于评估治疗反应和预测复发风险至关重要。微小RNA（miRNA）是在基因调控中起关键作用的小型非编码RNA，已成为JMML-MRD检测中有前景的生物标志物。本综述探讨了miRNA在JMML发病机制中的作用机制，强调了它们在诊断、预后和治疗方面的潜力。miRNA谱失调与不同的JMML亚组和疾病进展相关，提示其在非侵入性MRD监测中的应用价值。新出现的证据表明，miR-150-5p作为一种靶向STAT5b的肿瘤抑制因子，在改善JMML异常信号通路方面具有治疗潜力。我们将传统的MRD检测方法，如流式细胞术和聚合酶链反应（PCR），与基于miRNA的技术进行比较，强调了后者具有更高的敏感性、特异性和非侵入性。miRNA分析技术的最新进展，包括下一代测序和数字PCR，能够精确检测残留的白血病细胞，并支持个性化治疗方法。尽管取得了重大进展，但在标准化基于miRNA的检测方法及其临床应用验证方面仍存在挑战。包括患者隐私和知情同意在内的伦理考量，对于将miRNA诊断纳入常规医疗仍至关重要。本综述全面综合了当前关于JMML中miRNA特征的知识，阐明了它们在MRD监测中的变革潜力，并为创新治疗策略铺平了道路。
