Gene expression profiles predictive of outcome and age in infant acute lymphoblastic leukemia: a Children's Oncology Group study
Gene expression profiles predictive of outcome and age in infant acute lymphoblastic leukemia: a Children's Oncology Group study
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DOI：
10.1182/blood-2011-10-382861
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发表时间：
2012-02-23
期刊：
影响因子：
20.3
通讯作者：
Willman, Cheryl L.
中科院分区：
文献类型：
--
作者：
Kang, Huining;Wilson, Carla S.;Willman, Cheryl L.
对儿童肿瘤组试验 P9407 的 97 例婴儿 ALL 病例进行了基因表达谱分析。结果预测因子的统计模型揭示了 3 个基因，除了年龄和 MLL 状态外，还可以高度预测无事件生存期 (EFS)：FLT3、IRX2 和 TACC2。在一组预后良好的婴儿中发现了低 FLT3 表达（n = 11；5 年 EFS 为 100%），而 IRX2 和 TACC2 的差异表达将其余婴儿分为两组，生存率显着不同（5 年 EFS 分别为 16% 和 64%；P < .001）。当单独分析 MLL-AFF1 婴儿时，开发了一个 7 基因分类器，将其分为 2 个不同的组，结果显着不同（5 年 EFS 分别为 20% 和 65%；P < .001）。在此分类中，NEGR1 表达升高与较好的 EFS 相关，而 IRX2、EPS8 和 TPD52 表达与较差的结果相关。该分类器还预测了 Interfant-99 试验中独立婴儿 ALL 队列中的 EFS。当将表达谱作为相对于患者年龄的连续变量进行评估时，我们进一步发现小于或等于 90 天的婴儿和大于 90 天的婴儿的表达谱存在显着差异。这些与年龄相关的模式表明白血病发生的不同机制，并且可能是这些年龄组历史上出现的不同结果的基础。 （血。2012；119（8）：1872-1881）
Gene expression profiling was performed on 97 cases of infant ALL from Children's Oncology Group Trial P9407. Statistical modeling of an outcome predictor revealed 3 genes highly predictive of event-free survival (EFS), beyond age and MLL status: FLT3, IRX2, and TACC2. Low FLT3 expression was found in a group of infants with excellent outcome (n = 11; 5-year EFS of 100%), whereas differential expression of IRX2 and TACC2 partitioned the remaining infants into 2 groups with significantly different survivals (5-year EFS of 16% vs 64%; P < .001). When infants with MLL-AFF1 were analyzed separately, a 7-gene classifier was developed that split them into 2 distinct groups with significantly different outcomes (5-year EFS of 20% vs 65%; P < .001). In this classifier, elevated expression of NEGR1 was associated with better EFS, whereas IRX2, EPS8, and TPD52 expression were correlated with worse outcome. This classifier also predicted EFS in an independent infant ALL cohort from the Interfant-99 trial. When evaluating expression profiles as a continuous variable relative to patient age, we further identified striking differences in profiles in infants less than or equal to 90 days of age and those more than 90 days of age. These age-related patterns suggest different mechanisms of leukemogenesis and may underlie the differential outcomes historically seen in these age groups. (Blood. 2012; 119(8):1872-1881)