An 86-probe-set gene-expression signature predicts survival in cytogenetically normal acute myeloid leukemia
An 86-probe-set gene-expression signature predicts survival in cytogenetically normal acute myeloid leukemia
复制标题
DOI：
10.1182/blood-2008-02-134411
复制
发表时间：
2008-11-15
期刊：
影响因子：
20.3
通讯作者：
Buske, Christian
中科院分区：
文献类型：
--
作者：
Metzeler, Klaus H.;Hummel, Manuela;Buske, Christian
细胞遗传学正常的急性髓性白血病（CN-AML）患者显示出异质性的治疗结果。我们使用基因表达谱来开发预测CN-AML总生存期（OS）的基因特征。基于1999年德国AM-LCG试验中163例患者的数据，并对寡核苷酸微阵列进行分析，我们使用监督主成分分析来识别86个探针集（代表66个不同的基因），这些探针集与OS相关，并根据此特征定义预后评分。当应用于79例CN-AML患者的独立队列时，该连续评分仍然是OS（风险比[HR]，1.85; P=.002）、无事件生存期（HR = 1.73; P=.001）和无复发生存期（HR = 1.76; P=.025）的重要预测因子。在校正了年龄、FLT 3 ITD和NPM 1状态的多变量分析中，它保持了其预后价值。在CALGB研究9621中接受治疗的64例CN-AML患者的验证队列中，评分也预测OS（HR = 4.11; P
Patients with cytogenetically normal acute myeloid leukemia (CN-AML) show heterogeneous treatment outcomes. We used gene-expression profiling to develop a gene signature that predicts overall survival (OS) in CN-AML. Based on data from 163 patients treated in the German AM-LCG 1999 trial and analyzed on oligonucleotide microarrays, we used supervised principal component analysis to identify 86 probe sets (representing 66 different genes), which correlated with OS, and defined a prognostic score based on this signature. When applied to an independent cohort of 79 CN-AML patients, this continuous score remained a significant predictor for OS (hazard ratio [HR], 1.85; P=.002), event-free survival (HR = 1.73; P=.001), and relapse-free survival (HR = 1.76; P=.025). It kept its prognostic value in multivariate analyses adjusting for age, FLT3 ITD, and NPM1 status. In a validation cohort of 64 CN-AML patients treated on CALGB study 9621, the score also predicted OS (HR = 4.11; P