Willenbrock Klaus, Küppers Ralf, Renné Christoph, Brune Verena, Eckerle Susan, Weidmann Eckhart, Bräuninger Andreas, Hansmann Martin-Leo
Senckenbergisches Institut für Pathologie, Klinikum der Johann Wolfgang Goethe-Universität, Frankfurt am Main, Germany.
Haematologica. 2006 May;91(5):596-604.
Anaplastic large cell lymphoma (ALCL) and classical Hodgkin's lymphoma (HL) are derived from different cell types, namely T cells and B cells, respectively. However, both lymphomas share a similar cytological and immunohistochemical tumor cell phenotype with little resemblance to their cells of origin.
In this study, the transcriptional profiles of ALCL cell lines, primary ALCL tumor cells from peripheral blood and HL cell lines were compared to each other and to normal B-cell subsets, B non-Hodgkin's lymphomas (NHL) and B NHL- and Epstein-Barr virus (EBV)-transformed B-cell lines in order to establish their relationship at the transcriptional level and to identify genes with possible pathobiological impact. Expression of some of the genes identified was confirmed in microdissected primary tumor cells by reverse transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry.
HL samples clustered separately from ALCL samples, but HL and ALCL were found to be more closely related to each other than to any normal or malignant B-cell sample in the dataset. Their relationship was determined to a large extent, but not exclusively, by lack of expression of B-cell antigens and by the over-expression of mRNA encoding activation markers and structural proteins. Apart from established differences between HL and ALCL, further genes of interest could be identified that distinguish both entities from each other and from the other samples. The differential expression of PRAME, DDR2, SOCS3 and CEBPD in HL and ALCL was confirmed in primary tumor tissue by immunohistochemistry and/or RT-PCR.
At a transcriptional level HL is more closely related to Alk+ ALCL than to the B-NHL or B-cell samples investigated, although it is a B-cell derived lymphoma. The newly identified genes discriminating HL and ALCL may be pathobiologically important and may serve as possible therapeutic targets.
间变性大细胞淋巴瘤（ALCL）和经典型霍奇金淋巴瘤（HL）分别起源于不同的细胞类型，即T细胞和B细胞。然而，这两种淋巴瘤具有相似的细胞学和免疫组化肿瘤细胞表型，与其起源细胞几乎没有相似之处。
在本研究中，将ALCL细胞系、外周血原发性ALCL肿瘤细胞和HL细胞系的转录谱相互比较，并与正常B细胞亚群、B细胞非霍奇金淋巴瘤（NHL）以及B细胞NHL和爱泼斯坦-巴尔病毒（EBV）转化的B细胞系进行比较，以在转录水平上建立它们之间的关系，并鉴定可能具有病理生物学影响的基因。通过逆转录聚合酶链反应（RT-PCR）和免疫组化在显微切割的原发性肿瘤细胞中证实了一些鉴定出的基因的表达。
HL样本与ALCL样本分开聚类，但发现HL和ALCL彼此之间的关系比数据集中任何正常或恶性B细胞样本都更密切。它们之间的关系在很大程度上（但并非完全）由B细胞抗原的缺乏表达以及编码激活标志物和结构蛋白的mRNA的过表达所决定。除了HL和ALCL之间已确定的差异外，还可以鉴定出其他感兴趣的基因，这些基因可将这两种实体彼此区分开来，并与其他样本区分开来。通过免疫组化和/或RT-PCR在原发性肿瘤组织中证实了PRAME、DDR2、SOCS3和CEBPD在HL和ALCL中的差异表达。
在转录水平上，HL与ALK+ALCL的关系比与所研究的B-NHL或B细胞样本更密切，尽管它是一种B细胞来源的淋巴瘤。新鉴定出的区分HL和ALCL的基因可能在病理生物学上具有重要意义，并可能作为潜在的治疗靶点。
