Natkunam Yasodha, Zhao Shuchun, Mason David Y, Chen Jun, Taidi Behnaz, Jones Margaret, Hammer Anne S, Hamilton Dutoit Stephen, Lossos Izidore S, Levy Ronald
Department of Pathology, Stanford University School of Medicine, CA, USA, and Nuffield Department of Clinical Laboratory Sciences, John Radcliffe Hospital, Oxford, UK.
Blood. 2007 Feb 15;109(4):1636-42. doi: 10.1182/blood-2006-08-039024. Epub 2006 Oct 12.
We previously developed a multivariate model based on the RNA expression of 6 genes (LMO2, BCL6, FN1, CCND2, SCYA3, and BCL2) that predicts survival in diffuse large B-cell lymphoma (DLBCL) patients. Since LMO2 emerged as the strongest predictor of superior outcome, we generated a monoclonal anti-LMO2 antibody in order to study its tissue expression pattern. Immunohistologic analysis of over 1200 normal and neoplastic tissue and cell lines showed that LMO2 protein is expressed as a nuclear marker in normal germinal-center (GC) B cells and GC-derived B-cell lines and in a subset of GC-derived B-cell lymphomas. LMO2 was also expressed in erythroid and myeloid precursors and in megakaryocytes and also in lymphoblastic and acute myeloid leukemias. It was rarely expressed in mature T, natural killer (NK), and plasma cell neoplasms and was absent from nonhematolymphoid tissues except for endothelial cells. Hierarchical cluster analysis of immunohistologic data in DLBCL demonstrated that the expression profile of the LMO2 protein was similar to that of other GC-associated proteins (HGAL, BCL6, and CD10) but different from that of non-GC proteins (MUM1/IRF4 and BCL2). Our results warrant inclusion of LMO2 in multivariate analyses to construct a clinically applicable immunohistologic algorithm for predicting survival in patients with DLBCL.
我们之前基于6个基因(LMO2、BCL6、FN1、CCND2、SCYA3和BCL2)的RNA表达构建了一个多变量模型,用于预测弥漫性大B细胞淋巴瘤(DLBCL)患者的生存情况。由于LMO2是预后良好最强的预测因子,我们制备了一种抗LMO2单克隆抗体,以研究其组织表达模式。对1200多个正常和肿瘤组织及细胞系进行免疫组织学分析显示,LMO2蛋白在正常生发中心(GC)B细胞、GC来源的B细胞系以及一部分GC来源的B细胞淋巴瘤中作为核标志物表达。LMO2也在红系和髓系前体细胞、巨核细胞中表达,同样在淋巴细胞白血病和急性髓系白血病中表达。它在成熟T细胞、自然杀伤(NK)细胞和浆细胞瘤中很少表达,除内皮细胞外,在非血液淋巴组织中不表达。DLBCL免疫组织学数据的层次聚类分析表明,LMO2蛋白的表达谱与其他GC相关蛋白(HGAL、BCL6和CD10)相似,但与非GC蛋白(MUM1/IRF4和BCL2)不同。我们的结果支持将LMO2纳入多变量分析,以构建一种临床适用的免疫组织学算法,用于预测DLBCL患者的生存情况。