Clinical Utility of Microarray-Based Gene Expression Profiling in the Diagnosis and Subclassification of Leukemia: Report From the International Microarray Innovations in Leukemia Study Group
Clinical Utility of Microarray-Based Gene Expression Profiling in the Diagnosis and Subclassification of Leukemia: Report From the International Microarray Innovations in Leukemia Study Group
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DOI：
10.1200/jco.2009.23.4732
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发表时间：
2010-05-20
影响因子：
45.3
通讯作者：
Foa, Robin
中科院分区：
文献类型：
--
作者：
Haferlach, Torsten;Kohlmann, Alexander;Foa, Robin
目的：微阵列技术在白血病研究中的创新评估了基因表达谱作为一种单一测试将白血病亚型分为常规骨髓和淋巴恶性肿瘤的临床应用。方法在三大洲的11个实验室进行调查，包括3334例患者。一项探索性回顾性I期研究旨在发现生物标志物，并生成了2143例白血病和骨髓增生异常综合征患者的全基因组表达谱。在一项包含1191名患者的独立队列的前瞻性第二阶段研究中，进一步验证了基于基因表达谱的诊断准确性。结果在2096份样本的基础上，一期研究对所有18个不同类别的分类准确率达到92.2%（中位特异性为99.7%）。在第二个队列中，前瞻性收集了1152例患者，对14种急性白血病标准亚型（8种急性淋巴细胞白血病和6种急性髓系白血病，n = 693）的分类方案达到95.6%的中位敏感性和99.8%的中位特异性。在51例差异病例中，有29例（57%）的微阵列结果优于常规诊断方法。结论基因表达谱是一种可靠的血液恶性肿瘤诊断技术，具有较高的准确性。它可以补充当前的诊断算法，并为无法获得当今最先进诊断检查的患者提供可靠的平台。我们的综合基因表达数据集将提交给公共领域，以促进对白血病分子理解的研究。
PurposeThe Microarray Innovations in Leukemia study assessed the clinical utility of gene expression profiling as a single test to subtype leukemias into conventional categories of myeloid and lymphoid malignancies.MethodsThe investigation was performed in 11 laboratories across three continents and included 3,334 patients. An exploratory retrospective stage I study was designed for biomarker discovery and generated whole-genome expression profiles from 2,143 patients with leukemias and myelodysplastic syndromes. The gene expression profiling-based diagnostic accuracy was further validated in a prospective second study stage of an independent cohort of 1,191 patients.ResultsOn the basis of 2,096 samples, the stage I study achieved 92.2% classification accuracy for all 18 distinct classes investigated (median specificity of 99.7%). In a second cohort of 1,152 prospectively collected patients, a classification scheme reached 95.6% median sensitivity and 99.8% median specificity for 14 standard subtypes of acute leukemia (eight acute lymphoblastic leukemia and six acute myeloid leukemia classes, n = 693). In 29 (57%) of 51 discrepant cases, the microarray results had outperformed routine diagnostic methods.ConclusionGene expression profiling is a robust technology for the diagnosis of hematologic malignancies with high accuracy. It may complement current diagnostic algorithms and could offer a reliable platform for patients who lack access to today's state-of-the-art diagnostic work-up. Our comprehensive gene expression data set will be submitted to the public domain to foster research focusing on the molecular understanding of leukemias.