Department of Clinical Sciences and Community Health, University of Milano, Hematology 1, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy.
Blood. 2012 Aug 9;120(6):1274-81. doi: 10.1182/blood-2012-01-405555. Epub 2012 Jun 27.
Anaplastic large-cell lymphomas (ALCLs) are a group of clinically and biologically heterogeneous diseases including the ALK(+) and ALK(-) systemic forms. Whereas ALK(+) ALCLs are molecularly characterized and can be readily diagnosed, specific immunophenotypic or genetic features to define ALK(-) ALCL are missing, and their distinction from other T-cell non-Hodgkin lymphomas (T-NHLs) remains controversial. In the present study, we undertook a transcriptional profiling meta-analysis of 309 cases, including ALCL and other primary T-NHL samples. Pathway discovery and prediction analyses defined a minimum set of genes capable of recognizing ALK(-) ALCL. Application of quantitative RT-PCR in independent datasets from cryopreserved and formalin-fixed paraffin-embedded samples validated a 3-gene model (TNFRSF8, BATF3, and TMOD1) able to successfully separate ALK(-) ALCL from peripheral T-cell lymphoma not otherwise specified, with overall accuracy near 97%. In conclusion, our data justify the possibility of translating quantitative RT-PCR protocols to routine clinical settings as a new approach to objectively dissect T-NHL and to select more appropriate therapeutic protocols.
间变大细胞淋巴瘤（ALCLs）是一组临床上和生物学上具有异质性的疾病，包括 ALK(+) 和 ALK(-) 全身形式。虽然 ALK(+) ALCL 具有分子特征且易于诊断，但缺乏用于定义 ALK(-) ALCL 的特定免疫表型或遗传特征，并且其与其他 T 细胞非霍奇金淋巴瘤（T-NHL）的区分仍然存在争议。在本研究中，我们对 309 例病例进行了转录谱元分析，包括 ALCL 和其他原发性 T-NHL 样本。途径发现和预测分析定义了一组最小的基因，能够识别 ALK(-) ALCL。在来自冷冻和福尔马林固定石蜡包埋样本的独立数据集上应用定量 RT-PCR 验证了能够成功将 ALK(-) ALCL 与非特指外周 T 细胞淋巴瘤区分开来的 3 个基因模型（TNFRSF8、BATF3 和 TMOD1），总体准确率接近 97%。总之，我们的数据证明了将定量 RT-PCR 方案转化为常规临床环境的可能性，作为一种客观剖析 T-NHL 和选择更合适治疗方案的新方法。
