Microarray-based classification of a consecutive series of 121 childhood acute leukemias: prediction of leukemic and genetic subtype as well as of minimal residual disease status
Microarray-based classification of a consecutive series of 121 childhood acute leukemias: prediction of leukemic and genetic subtype as well as of minimal residual disease status
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DOI：
10.1038/sj.leu.2404688
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发表时间：
2007-06-01
期刊：
影响因子：
11.4
通讯作者：
Fioretos, T.
中科院分区：
文献类型：
--
作者：
Andersson, A.;Ritz, C.;Fioretos, T.
对 121 例连续儿童白血病（87 例 B 系急性淋巴细胞白血病 (ALL)、11 例 T 细胞 ALL 和 23 例急性髓性白血病 (AML)）进行了基因表达分析，这些研究是在一个中心进行的 8 年期间进行的。利用监督学习算法 k-近邻构建基因表达预测器，可以根据临床重要亚型对 ALL/AML 进行高精度分类。独立数据集中的验证实验验证了我们的分类器的高预测精度。具有非典型细胞遗传学畸变或具有正常核型的 B 谱系 ALL 表现出异质性基因表达谱，导致预测准确性较低。第 29 天 MRD 较高 (40.1%) 的 T 细胞 ALL 的微小残留病状态 (MRD) 在诊断时就可以 100% 准确度进行分类。在具有异常细胞遗传学畸变或正常核型的儿童白血病中，无监督分析确定了两个新的亚组：一个主要由仍处于完全缓解（CR）的病例组成，另一个包含少数处于 CR 的患者以及除一名患者外的所有患者复发。这项对一系列儿童白血病的连续研究证实并进一步扩展了先前的报告，表明全局基因表达谱为儿童白血病的遗传和临床分类提供了宝贵的工具。
Gene expression analyses were performed on 121 consecutive childhood leukemias (87 B-lineage acute lymphoblastic leukemias (ALLs), 11 T-cell ALLs and 23 acute myeloid leukemias (AMLs)), investigated during an 8-year period at a single center. The supervised learning algorithm k-nearest neighbor was utilized to build gene expression predictors that could classify the ALLs/AMLs according to clinically important subtypes with high accuracy. Validation experiments in an independent data set verified the high prediction accuracies of our classifiers. B-lineage ALLs with uncharacteristic cytogenetic aberrations or with a normal karyotype displayed heterogeneous gene expression profiles, resulting in low prediction accuracies. Minimal residual disease status (MRD) in T-cell ALLs with a high (40.1%) MRD at day 29 could be classified with 100% accuracy already at the time of diagnosis. In pediatric leukemias with uncharacteristic cytogenetic aberrations or with a normal karyotype, unsupervised analysis identified two novel subgroups: one consisting mainly of cases remaining in complete remission (CR) and one containing a few patients in CR and all but one of the patients who relapsed. This study of a consecutive series of childhood leukemias confirms and extends further previous reports demonstrating that global gene expression profiling provides a valuable tool for genetic and clinical classification of childhood leukemias.