Marcucci Guido, Maharry Kati, Whitman Susan P, Vukosavljevic Tamara, Paschka Peter, Langer Christian, Mrózek Krzysztof, Baldus Claudia D, Carroll Andrew J, Powell Bayard L, Kolitz Jonathan E, Larson Richard A, Bloomfield Clara D
Division of Hematology and Oncology, Department of Internal Medicine, Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA.
J Clin Oncol. 2007 Aug 1;25(22):3337-43. doi: 10.1200/JCO.2007.10.8720. Epub 2007 Jun 18.
To validate ERG overexpression as an adverse predictor and assess its prognostic value in the context of other molecular markers in cytogenetically normal (CN) -acute myeloid leukemia (AML).
Seventy-six adult patients with primary CN-AML, younger than 60 years and treated on Cancer and Leukemia Group B (CALGB) trial 19808, were evaluated for ERG expression by quantitative reverse transcriptase polymerase chain reaction. They were then combined with 72 patients enrolled onto CALGB 9621 for analyses that included other molecular markers.
Similar to patients enrolled onto CALGB 9621, high ERG expressers on CALGB 19808 had fewer complete remissions (CRs; P = .03) and worse event-free survival (EFS; P = .016) than low ERG expressers. In the combined set, high expressers (n = 55) had fewer CRs (P = .004) and shorter EFS (P < .001) than low expressers (n = 93). High ERG predicted failure to achieve CR (P = .004) after adjusting for BAALC expression (P = .04) and age (P = .008), and EFS (P = .004) after adjusting for FLT3 internal tandem duplication (ITD; P < .001). Among patients without FLT3-ITD (FLT3-ITD negative), only high ERG predicted shorter EFS (P = .001). Among NPM1-mutated (NPM1 positive) patients, high ERG predicted shorter EFS (P = .003), after adjusting for FLT3-ITD (P < .001). When all three markers were considered together, in the favorable FLT3-ITD-negative/NPM1-positive subset, high ERG was the only factor predicting shorter EFS (P = .002).
We validated ERG overexpression as an adverse predictor in CN-AML. Moreover, by using ERG expression levels, we improved the previously proposed molecular-risk classification of CN-AML based on the presence or absence of FLT3-ITD and NPM1 mutations, given that we identified subsets with different outcome among FLT3-ITD-negative, NPM1-positive, and FLT3-ITD-negative/NPM1-positive patients.
验证ERG过表达作为一种不良预后指标，并在细胞遗传学正常（CN）的急性髓系白血病（AML）中，结合其他分子标志物评估其预后价值。
对76例年龄小于60岁、接受癌症与白血病B组（CALGB）19808试验治疗的原发性CN-AML成年患者，通过定量逆转录聚合酶链反应评估ERG表达。然后将他们与72例纳入CALGB 9621的患者合并，进行包括其他分子标志物的分析。
与纳入CALGB 9621的患者相似，CALGB 19808试验中ERG高表达者的完全缓解（CR）率较低（P = 0.03），无事件生存期（EFS）较差（P = 0.016）。在合并队列中，ERG高表达者（n = 55）的CR率低于低表达者（n = 93）（P = 0.004），EFS较短（P < 0.001）。在调整BAALC表达（P = 0.04）和年龄（P = 0.008）后，高ERG表达预测无法达到CR（P = 0.004）；在调整FLT3内部串联重复（ITD；P < .001）后，高ERG表达预测EFS较差（P = 0.004）。在无FLT3-ITD（FLT3-ITD阴性）的患者中，只有高ERG表达预测EFS较短（P = 0.001）。在NPM1突变（NPM1阳性）的患者中，调整FLT3-ITD（P < 0.001）后，高ERG表达预测EFS较短（P = 0.003）。当同时考虑这三个标志物时，在预后良好的FLT3-ITD阴性/NPM1阳性亚组中，高ERG表达是预测EFS较短的唯一因素（P = 0.002）。
我们验证了ERG过表达是CN-AML的不良预后指标。此外，通过使用ERG表达水平，我们改进了先前基于FLT3-ITD和NPM1突变的有无对CN-AML进行的分子风险分类，因为我们在FLT3-ITD阴性、NPM1阳性以及FLT3-ITD阴性/NPM1阳性患者中识别出了具有不同预后的亚组。
