Gene expression profiling of pediatric acute myelogenous leukemia
Gene expression profiling of pediatric acute myelogenous leukemia
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DOI：
10.1182/blood-2004-03-1154
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发表时间：
2004-12-01
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;Mahfouz, R;Downing, JR
儿童急性髓性白血病（AML）的当代治疗需要将患者分配到特定的风险组。为了探索白血病原始细胞的表达谱是否可以准确区分AML的已知风险组，我们使用Affytek U133 A微阵列分析了130名儿童和20名成人AML诊断骨髓或外周血样本。对儿童AML的每种主要预后亚型确定了类别区分基因，包括t（15;17）[PML-RAR α]、t（8;21）[AML 1-ETO]、inv（16）[CBFbeta-MYH 11]、MLL嵌合融合基因和归类为FAB-M7的病例。当这些基因的子集用于监督学习算法时，实现了超过93%的总体分类准确率。此外，我们能够使用从儿科样本中产生的表达特征来准确地分类具有相同遗传病变的成人新发AML。类区分基因也为这些白血病的分子病理学提供了新的见解。最后，使用130例AML和137例急性淋巴细胞白血病的合并儿科数据集，我们确定了MLL嵌合融合基因病例的表达特征，与谱系无关。令人惊讶的是，含有MLL的部分串联重复的AML未能与MLL嵌合融合基因病例聚类，这表明它们的潜在转化机制存在显著差异。(C)2004年，美国血液学会。
Contemporary treatment of pediatric acute myeloid leukemia (AML) requires the assignment of patients to specific risk groups. To explore whether expression profiling of leukemic blasts could accurately distinguish between the known risk groups of AML, we analyzed 130 pediatric and 20 adult AML diagnostic bone marrow or peripheral blood samples using the Affymetrix U133A microarray. Class discriminating genes were identified for each of the major prognostic subtypes of pediatric AML, including t(15;17)[PML-RARalpha], t(8;21)[AML1-ETO], inv(16)[CBFbeta-MYH11], MLL chimeric fusion genes, and cases classified as FAB-M7. When subsets of these genes were used in supervised learning algorithms, an overall classification accuracy of more than 93% was achieved. Moreover, we were able to use the expression signatures generated from the pediatric samples to accurately classify adult de novo AMLs with the same genetic lesions. The class discriminating genes also provided novel insights into the molecular pathobiology of these leukemias. Finally, using a combined pediatric data set of 130 AMLs and 137 acute lymphoblastic leukemias, we identified an expression signature for cases with MLL chimeric fusion genes irrespective of lineage. Surprisingly, AMLs containing partial tandem duplications of MLL failed to cluster with MLL chimeric fusion gene cases, suggesting a significant difference in their underlying mechanism of transformation. (C) 2004 by The American Society of Hematology.