Identification of novel molecular prognostic markers for paediatric T-cell acute lymphoblastic leukaemia
Identification of novel molecular prognostic markers for paediatric T-cell acute lymphoblastic leukaemia
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DOI：
10.1111/j.1365-2141.2007.06576.x
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发表时间：
2007-05-01
影响因子：
6.5
通讯作者：
Kees, Ursula R.
中科院分区：
文献类型：
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作者：
Gottardo, Nicholas G.;Hoffmann, Katrin;Kees, Ursula R.
在过去的四十年里，新诊断的儿童T细胞急性淋巴细胞白血病（T-ALL）患者的生存率有了显着提高。与此形成鲜明对比的是，复发性T-ALL的预后仍然很差。我们试图确定基因表达谱是否可以揭示T-ALL儿童结局的特征。使用治疗开始前获得的12例患者标本，我们通过寡核苷酸微阵列检测了基因表达谱。我们确定了三个基因，CFLAR，NOTCH 2和BTG 3，其在诊断时的表达根据疾病结果准确区分患者。这些基因参与细胞凋亡和细胞增殖的调节。采用实时定量逆转录聚合酶链反应对25例儿童T-ALL患者进行独立队列研究，评估这三个预测基因的预后价值。不良结局组患者的累积复发率显著高于良好结局组患者（46% vs. 8%，P = 0.029）。不良结局组患者的5年总生存率也显著更差（P = 0.0039）。多变量分析证实了3基因预测因子的独立影响。我们的研究提供了全基因组表达谱可以检测儿科T-ALL中新的分子预后标志物的原则证据。
In the last four decades the survival of patients with newly diagnosed childhood T-cell acute lymphoblastic leukaemia (T-ALL) has improved dramatically. In sharp contrast, relapsed T-ALL continues to confer a dismal prognosis. We sought to determine if gene expression profiling could uncover a signature of outcome for children with T-ALL. Using 12 patient specimens obtained before therapy started, we examined the gene expression profile by oligonucleotide microarrays. We identified three genes, CFLAR, NOTCH2 and BTG3, whose expression at the time of diagnosis accurately distinguished the patients according to disease outcome. These genes are involved in the regulation of apoptosis and cellular proliferation. The prognostic value of the three predictive genes was assessed in an independent cohort of 25 paediatric T-ALL patients using quantitative real-time reverse transcription polymerase chain reaction. Patients assigned to the adverse outcome group had a significantly higher cumulative incidence of relapse compared with patients assigned to the favourable outcome group (46% vs. 8%, P = 0.029). Five-year overall survival was also significantly worse in the patients assigned to the adverse outcome group (P = 0.0039). The independent influence of the 3-gene predictor was confirmed by multivariate analysis. Our study provides proof of principle that genome-wide expression profiling can detect novel molecular prognostic markers in paediatric T-ALL.