Gene expression factors as predictors of genetic risk and survival in chronic lymphocytic leukemia
Gene expression factors as predictors of genetic risk and survival in chronic lymphocytic leukemia
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DOI：
10.3324/haematol.2009.010298
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发表时间：
2010-01-01
期刊：
影响因子：
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通讯作者：
Stilgenbauer, Stephan
中科院分区：
文献类型：
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作者：
Kienle, Dirk;Benner, Axel;Stilgenbauer, Stephan
背景基于基因表达分析，慢性淋巴细胞白血病的遗传特征和预后的替代标志物有很多。以往的研究主要集中在单个标记物和选定的疾病特征，这使得很难估计新标记物的相对价值。因此，在本研究中，选择了一个全面的方法，调查18个有前途的，部分新的表达标志物，在一个良好的特征队列的患者长期的临床随访和完整的遗传信息（IGHV状态，基因组异常）design and Methodsexpression markers进行了评估，使用实时定量逆转录酶聚合酶链反应在CD 19（+）纯化的样品从151例患者。进行多变量分析，以测试标记物的能力，以确定患者的遗传风险和预后标记的背景下建立的预后factors.ResultsFor个别标记，ZAP 70的表达提供了最高的正确分配率（81%）的患者的遗传风险（IGHV未突变，V3-21的使用，11 q-或17 p-），其次是LPL和TCF 7（均为76%）。利用ZAP 70、TCF 7、DMD、ATM四个基因组合的信息，将基因定位率提高到88%。在无治疗生存期的多因素分析中，IGHV突变状态和ADAM 29表达除了疾病分期外，还具有独立的预后价值。关于总生存率，ATM，ADAM 29，TCL 1和SEPT 10的表达提供了预后信息，除了来自临床和遗传factors.ConclusionsGene表达标志物是适合筛选，但不作为替代品的信息遗传风险因素。虽然许多个体标记物可能与结果相关，但只有少数具有独立的预后意义。在预后评估方面，基因预后因素不能被表达标志物所取代。
BackgroundA variety of surrogate markers for genetic features and outcome have been described in chronic lymphocytic leukemia based on gene expression analyses. Previous studies mostly focused on individual markers and selected disease characteristics, which makes it difficult to estimate the relative value of the novel markers. Therefore, in the present study a comprehensive approach was chosen investigating 18 promising, partly novel expression markers in a well characterized cohort of patients with long clinical follow-up and full genetic information (IGHV status, genomic abnormalities).Design and MethodsExpression markers were evaluated using real-time quantitative reverse transcriptase polymerase chain reaction in CD19(+)-purified samples from 151 patients. Multivariate analyses were performed to test the markers' ability to identify patients at genetic risk and as prognostic markers in the context of established prognostic factors.ResultsFor individual markers, ZAP70 expression provided the highest rate (81%) of correct assignment of patients at genetic risk (IGHV unmutated, V3-21 usage, 11q- or 17p-), followed by LPL and TCF7 (76% both). The assignment rate was improved to 88% by information from a four-gene combination (ZAP70, TCF7, DMD, ATM). In multivariate analysis of treatment-free survival, IGHV mutation status and expression of ADAM29 were of independent prognostic value besides disease stage. With regards to overall survival, expression of ATM, ADAM29, TCL1, and SEPT10 provided prognostic information in addition to that derived from clinical and genetic factors.ConclusionsGene expression markers are suitable for screening but not as surrogates for the information from genetic risk factors. While many individual markers may be associated with outcome, only a few are of independent prognostic significance. With regard to prognosis estimation, the genetic prognostic factors cannot be replaced by the expression markers.