Impact of mTOR expression on clinical outcome in paediatric patients with B-cell acute lymphoblastic leukaemia – preliminary report

Edyta Ulińska, Katarzyna Mycko, Elżbieta Sałacińska-Łoś, A. Pastorczak, A. Siwicka, W. Młynarski, M. Matysiak
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引用次数: 5

Abstract

Aim of the study To characterise expression of mTOR (mammalian target of rapamycin) in childhood B-cell acute lymphoblastic leukaemia (ALL), and to evaluate a possible link between mTOR and clinical characteristics. Material and methods The examined group consisted of 21 consecutive patients, aged 1–18 years, diagnosed with B-cell ALL in 2010, and 10 relapsed B-cell ALL patients diagnosed for the first time between 2009 and 2011, who developed relapse before 2014. All subjects were treated in the Department of Paediatric Haematology and Oncology of the Medical University of Warsaw according to the ALL-IC BFM 2002 Protocol. We evaluated mTOR and phospho-mTOR expression by immunohistochemistry using rabbit monoclonal antibodies. Results mTOR expression was found to be significantly associated with the risk of relapse and was more frequent in ALL recurrence. No significant relationship was detected between mTOR expression and other features of high-risk disease in paediatric ALL. Conclusions mTOR activity could be considered a high-risk feature in paediatric B-cell ALL. Expression of mTOR kinase is observed remarkably more frequently in disease recurrence than at first diagnosis, indicating higher proliferative and survival potential of leukaemic cells in relapse. Routine analysis of mTOR activity could be performed to select patients that may potentially benefit from mTOR inhibitors (MTI) treatment.
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mTOR表达对儿童b细胞急性淋巴细胞白血病患者临床预后的影响——初步报告
研究目的:研究mTOR(哺乳动物雷帕霉素靶蛋白)在儿童b细胞急性淋巴细胞白血病(ALL)中的表达,并评估mTOR与临床特征之间的可能联系。材料与方法实验组包括21例2010年诊断为b细胞ALL的连续患者,年龄1-18岁,以及10例2009 - 2011年首次诊断,2014年之前复发的b细胞ALL患者。所有受试者在华沙医科大学儿科血液学和肿瘤学系根据All - ic BFM 2002年议定书进行治疗。我们利用兔单克隆抗体免疫组化检测mTOR和磷酸化mTOR的表达。结果mTOR表达与ALL复发风险显著相关,在ALL复发中更为常见。未发现mTOR表达与儿科ALL高危疾病的其他特征有显著关系。结论mTOR活性可被认为是儿童b细胞ALL的高危特征。mTOR激酶的表达在疾病复发时比首次诊断时更为频繁,这表明复发时白血病细胞的增殖和生存潜力更高。可以对mTOR活性进行常规分析,以选择可能从mTOR抑制剂(MTI)治疗中获益的患者。
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