Identification of a global gene expression signature of B-chronic lymphocytic leukemia.
Identification of a global gene expression signature of B-chronic lymphocytic leukemia.
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发表时间：
2003-03
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通讯作者：
D. Jelinek;R. Tschumper;G. Stolovitzky;S. Iturria;Y. Tu;J. Lepre;Nigam H. Shah;N. Kay
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作者：
D. Jelinek;R. Tschumper;G. Stolovitzky;S. Iturria;Y. Tu;J. Lepre;Nigam H. Shah;N. Kay
慢性B淋巴细胞白血病(B-CLL)是一种成人起病的白血病，其特征是大量聚集抗凋亡的单克隆性B淋巴细胞。在这项研究中，我们对10名年龄匹配的健康人的B细胞和38名B-CLL患者的CLL B细胞进行了基因表达谱分析，以确定CLL和正常B细胞之间的关键遗传差异。此外，我们利用最近的独立研究来评估我们的分子B-CLL签名的重复性。我们使用了几种数据分析方法的新组合，包括我们自己的软件，确定了70个以前未报道的区分白血病细胞和正常B细胞的基因，以及最近报道的另外10个基因的B-CLL特异性表达水平。重要的是，这些基因中的许多以前已经与其他癌症相关联，从而进一步支持了它们作为导致B-CLL发病的候选基因的重要性。我们还使用独立的方法验证了这些基因的一个子集。此外，我们还证明，我们的基因可以用来创建诊断签名，在21名B-CLL和20名正常受试者的独立队列中以完美的敏感性和特异性执行，从而有力地验证了我们这组基因的信息性。最后，我们确定了一组区分低风险(RAI阶段0)和高风险(RAI阶段4)患者的31个基因，这表明可能还存在与疾病进展相关的基因表达特征。
B-chronic lymphocytic leukemia (B-CLL) is an adult-onset leukemia characterized by significant accumulation of apoptosis-resistant monoclonal B lymphocytes. In this study, we performed gene expression profiling on B cells obtained from 10 healthy age-matched individuals and CLL B cells from 38 B-CLL patients to identify key genetic differences between CLL and normal B cells. In addition, we leveraged recent independent studies to assess the reproducibility of our molecular B-CLL signature. We used a novel combination of several methods of data analysis including our own software and identified 70 previously unreported genes that differentiate leukemic cells from normal B cells, as well as confirmed recently reported B-CLL specific expression levels of an additional 10 genes. Importantly, many of these genes have previously been linked with other cancers, thus lending further support to their importance as candidate genes leading to B-CLL pathogenesis. We have also validated a subset of these genes using independent methodologies. Moreover, we show that our genes can be used to create a diagnostics signature that performs with perfect sensitivity and specificity in an independent cohort of 21 B-CLL and 20 normal subjects, thus strongly validating the informative nature of our set of genes. Finally, we identified a group of 31 genes that distinguish between low (Rai stage 0) and high (Rai stage 4) risk patients, suggesting that there may also be a gene expression signature that associates with disease progression.