Piatopoulou Despina, Avgeris Margaritis, Marmarinos Antonios, Xagorari Marieta, Baka Margarita, Doganis Dimitrios, Kossiva Lydia, Scorilas Andreas, Gourgiotis Dimitrios
Laboratory of Clinical Biochemistry-Molecular Diagnostics, 2nd Department of Pediatrics, Medical School, National and Kapodistrian University of Athens, 'P &A Kyriakou' Children's Hospital, Levadias 13 Street, Athens 11527, Greece.
Faculty of Biology, Department of Biochemistry and Molecular Biology, National and Kapodistrian University of Athens, Panepistimiopolis, Athens 15701, Greece.
Br J Cancer. 2017 Sep 5;117(6):801-812. doi: 10.1038/bjc.2017.256. Epub 2017 Aug 8.
Despite the favourable survival rates of childhood acute lymphoblastic leukaemia (ALL), a significant number of patients present resistance to antileukaemic agents and dismal prognosis. In this study, we analysed miR-125b expression in childhood ALL and evaluated its clinical utility for patients treated with Berlin-Frankfurt-Münster (BFM) protocol.
The study included 272 bone marrow specimens obtained on diagnosis and on BFM day 33 from 125 patients and 64 healthy children. Following extraction, RNA was polyadenylated and reverse transcribed. miR-125b levels were quantified by quantitative PCR. Cytogenetics, immunohistotype and MRD were analysed according to international guidelines.
Downregulated miR-125b levels were detected in childhood ALL patients and correlated with adverse prognosis. Following BFM induction, miR-125b levels were significantly increased, however, elevated day 33/diagnosis miR-125b ratio was associated with unfavourable disease features. Loss of miR-125b during diagnosis and higher day 33/diagnosis ratio were correlated with stronger risk for disease short-term relapse and patients' worse survival. Moreover, multivariate regression models highlighted the independent prognostic value of miR-125b for childhood ALL. Finally, the combination of miR-125b with clinically used disease markers clearly enhanced the prediction of patients' resistance to BFM chemotherapy.
miR-125b significantly improves the prognosis of childhood ALL patients' outcome under BFM treatment.
尽管儿童急性淋巴细胞白血病（ALL）患者生存率良好，但仍有相当数量的患者对抗白血病药物耐药，预后不佳。在本研究中，我们分析了儿童ALL中miR-125b的表达，并评估其对接受柏林-法兰克福-明斯特（BFM）方案治疗患者的临床应用价值。
本研究纳入了125例患者和64名健康儿童在诊断时及BFM方案治疗第33天采集的272份骨髓标本。提取RNA后进行聚腺苷酸化和逆转录。通过定量PCR对miR-125b水平进行定量分析。根据国际指南分析细胞遗传学、免疫组化类型和微小残留病（MRD）。
在儿童ALL患者中检测到miR-125b水平下调，且与不良预后相关。BFM诱导治疗后，miR-125b水平显著升高，然而，第33天/诊断时miR-125b比值升高与不良疾病特征相关。诊断时miR-125b缺失以及第33天/诊断时比值较高与疾病短期复发风险增加和患者生存较差相关。此外，多变量回归模型突出了miR-125b对儿童ALL的独立预后价值。最后，miR-125b与临床使用的疾病标志物联合使用明显增强了对患者BFM化疗耐药性的预测。
miR-125b显著改善了接受BFM治疗的儿童ALL患者的预后。
