Expression data from ALL samples for patients included in the Dutch Childhood Oncology Group

Childhood acute lymphoblastic leukemia (ALL) comprises a large group of genetic subtypes with a favorable prognosis characterized by a TEL-AML1-fusion, hyperdiploidy (>50 chromosomes) or E2A-PBX1 fusion and a smaller group with unfavorable outcome characterized by either a BCR-ABL-fusion, MLL-rearrangement or T-ALL. About 25% of precursor B-ALL are currently genetically unclassified and have an intermediate prognosis. The present study used genome-wide strategies to reveal new biological insights and advance the prognostic classification of childhood ALL. A double-loop cross validation was used to construct a classifier based on gene expression in ALL cells from 190 newly diagnosed cases (COALL cohort, GEO GSE13425) with a prediction accuracy of 90%. T-ALL, TEL-AML1-positive, hyperdiploid and E2A-rearranged cases were identified with 100% sensitivity and ≥94% specificity. The classifier accuracy was confirmed in an independent cohort of 107 cases (87.9%, DCOG cohort, GEO GSE13351). Keywords: gene expression study for classification of ALL subtypes Bone marrow and peripheral blood samples were collected at diagnosis and frozen. After thawing, RNA was extracted, labelled and hybridized to Affymetrix U133 Plus 2.0 arrays.

儿童急性淋巴细胞白血病（Childhood acute lymphoblastic leukemia, ALL）包含一大类预后良好的遗传亚型，这类亚型以TEL-AML1融合基因（TEL-AML1-fusion）、超二倍体（染色体数目＞50）或E2A-PBX1融合基因为特征；另有一小类亚型预后不良，其特征为携带BCR-ABL融合基因（BCR-ABL-fusion）、发生MLL重排（MLL-rearrangement）或为T细胞急性淋巴细胞白血病（T-ALL）。目前约25%的前体B细胞急性淋巴细胞白血病尚未明确遗传学分类，预后处于中等水平。本研究采用全基因组组学策略，揭示了儿童ALL的全新生物学机制，并推动了其预后分型体系的完善。本研究针对190例新诊断的ALL病例（COALL队列，GEO数据库GSE13425）的ALL细胞基因表达数据，采用双环交叉验证方法构建分类器，其预测准确率达90%。对于T-ALL、TEL-AML1融合基因阳性、超二倍体及E2A重排的病例，该分类器的识别灵敏度达100%，特异性≥94%。该分类器的准确率在107例独立验证队列中得到证实（准确率87.9%，DCOG队列，GEO数据库GSE13351）。关键词：急性淋巴细胞白血病亚型分类基因表达研究。研究样本采集自诊断时的骨髓及外周血，冻存保存。样本解冻后提取RNA，经标记后与Affymetrix U133 Plus 2.0基因芯片进行杂交。