FLT3 gene-expression signature in normal karyotype AML

Acute myeloid leukemia with normal karyotype (NK-AML) represents a cytogenetic grouping with intermediate prognosis but substantial molecular and clinical heterogeneity. Within this subgroup, presence of FLT3 (FMS-like tyrosine kinase 3) internal tandem duplication (ITD) mutation predicts less favorable outcome. The goal of our study was to discover gene-expression patterns correlated with FLT3-ITD mutation, and to evaluate the utility of a FLT3 signature for prognostication. The dataset comprises gene-expression profiles of 137 normal karyotype acute myeloid leukemia (NK-AML) specimens carried out using Stanford cDNA microarrays, to accompany the study of L Bullinger et al. For each array, Channel 2 represents Cy5-labeled NK-AML RNA, and Channel 1 Cy3-labeled universal reference RNA. Keywords: Logical Set DNA microarrays were used to profile gene expression in a training set of 65 NK-AML cases. Supervised analysis was applied to build a gene expression-based predictor of FLT3-ITD mutation status. The predictor was then evaluated by classifying expression profiles from an independent test set of 72 NK-AML cases.

核型正常型急性髓系白血病（acute myeloid leukemia with normal karyotype, NK-AML）是一类细胞遗传学分组，其预后风险处于中等水平，但存在显著的分子与临床异质性。在该亚组中，FMS样酪氨酸激酶3（FMS-like tyrosine kinase 3, FLT3）内部串联重复（internal tandem duplication, ITD）突变提示患者预后不良。本研究旨在发掘与FLT3-ITD突变相关的基因表达模式，并评估FLT3特征标签用于预后预测的应用价值。本数据集包含137份核型正常型急性髓系白血病（NK-AML）样本的基因表达谱，采用斯坦福cDNA微阵列（Stanford cDNA microarrays）进行检测，作为Bullinger等人该项研究的配套数据集。每份芯片的2号通道代表Cy5标记的NK-AML RNA，1号通道代表Cy3标记的通用参考RNA。关键词：逻辑集合型DNA微阵列。本研究采用逻辑集合型DNA微阵列对由65例NK-AML病例组成的训练集进行基因表达谱分析，通过监督分析构建基于基因表达的FLT3-ITD突变状态预测模型。随后，针对包含72例NK-AML病例的独立测试集的表达谱进行分类，以此评估该预测模型的效能。