Classification of pediatric acute lymphoblastic leukemia by gene expression profiling
Classification of pediatric acute lymphoblastic leukemia by gene expression profiling
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DOI：
10.1182/blood-2003-01-0338
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发表时间：
2003-10-15
期刊：
影响因子：
20.3
通讯作者：
Downing, JR
中科院分区：
文献类型：
--
作者：
Ross, ME;Zhou, XD;Downing, JR
儿童急性淋巴细胞白血病（ALL）的当代治疗需要将患者分配到特定的危险群体。我们最近证明，白血病原细胞的表达谱可以准确地识别已知的ALL预后亚型，包括t细胞谱系ALL （T-ALL）、E2A-PBX1、TEL-AML1、MLL重排、BCR-ABL和超过50条染色体的超二倍体核型。作为将该方法发展为一线诊断工具的下一步，我们现在已经使用高密度寡核苷酸阵列分析了来自132个诊断样本的白血病原细胞，该阵列允许对人类基因组中大多数已鉴定的基因进行询问。近60%新发现的亚型区分基因是我们之前研究中未发现的新标记，因此应该为这些白血病背后的改变生物学提供新的见解。此外，新选择的一部分基因被高度列为类别判别器，当纳入类别预测算法时，总体诊断准确率达到97%。现在应该在一线临床试验中评估包含已识别的鉴别基因的阵列的性能，以确定该方法在临床环境中的准确性、实用性和成本效益。（Blood. 2003; 102:2951-2959） (C) 2003年由美国血液学会出版。
Contemporary treatment of pediatric acute lymphoblastic leukemia (ALL) requires the assignment of patients to specific risk groups. We have recently demonstrated that expression profiling of leukemic blasts can accurately identify the known prognostic subtypes of ALL, including T-cell lineage ALL (T-ALL), E2A-PBX1, TEL-AML1, MLL rearrangements, BCR-ABL, and hyperdiploid karyotypes with more than 50 chromosomes. As the next step toward developing this methodology into a frontline diagnostic tool, we have now analyzed leukemic blasts from 132 diagnostic samples using higher density oligonucleotide arrays that allow the interrogation of most of the identified genes in the human genome. Nearly 60% of the newly identified subtype discriminating genes are novel markers not identified in our previous study, and thus should provide new insights into the altered biology underlying these leukemias. Moreover, a proportion of the newly selected genes are highly ranked as class discriminators, and when incorporated into class-predicting algorithms resulted in an overall diagnostic accuracy of 97%. The performance of an array containing the identified discriminating genes should now be assessed in frontline clinical trials in order to determine the accuracy, practicality, and cost effectiveness of this methodology in the clinical setting. (Blood. 2003; 102:2951-2959) (C) 2003 by The American Society of Hematology.