Zhang Y, Ohyashiki J H, Takaku T, Shimizu N, Ohyashiki K
First Department of Internal Medicine, Tokyo Medical University, Tokyo, Japan.
Br J Cancer. 2006 Feb 27;94(4):599-608. doi: 10.1038/sj.bjc.6602968.
Nasal NK/T-cell lymphoma is an aggressive subtype of non-Hodgkin lymphoma (NHL) that is closely associated with Epstein-Barr virus (EBV). The clonal expansion of EBV-infected NK or T cells is also seen in patients with chronic active EBV (CAEBV) infection, suggesting that two diseases might share a partially similar mechanism by which EBV affects host cellular gene expression. To understand the pathogenesis of EBV-associated NK/T-cell lymphoproliferative disorders (LPD) and design new therapies, we employed a novel EBV DNA microarray to compare patterns of EBV expression in six cell lines established from EBV-associated NK/T-cell LPD. We found that expression of BZLF1, which encodes the immediate-early gene product Zta, was expressed in SNK/T cells and the expression levels were preferentially high in cell lines from CAEBV infection. We also analyzed the gene expression patterns of host cellular genes using a human oligonucleotide DNA microarray. We identified a subset of pathogenically and clinically relevant host cellular genes, including TNFRSF10D, CDK2, HSPCA, IL12A as a common molecular biological properties of EBV-associated NK/T-cell LPD and a subset of genes, such as PDCD4 as a putative contributor for disease progression. This study describes a novel approach from the aspects of viral and host gene expression, which could identify novel therapeutic targets in EBV-associated NK/T-cell LPD.
鼻型NK/T细胞淋巴瘤是非霍奇金淋巴瘤（NHL）的一种侵袭性亚型，与爱泼斯坦-巴尔病毒（EBV）密切相关。慢性活动性EBV（CAEBV）感染患者中也可见EBV感染的NK或T细胞的克隆性扩增，这表明这两种疾病可能共享部分相似的机制，即EBV影响宿主细胞基因表达的机制。为了了解EBV相关的NK/T细胞淋巴增殖性疾病（LPD）的发病机制并设计新的治疗方法，我们采用了一种新型的EBV DNA微阵列来比较从EBV相关的NK/T细胞LPD建立的六个细胞系中EBV的表达模式。我们发现，编码即刻早期基因产物Zta的BZLF1在SNK/T细胞中表达，且在CAEBV感染的细胞系中表达水平优先较高。我们还使用人类寡核苷酸DNA微阵列分析了宿主细胞基因的基因表达模式。我们鉴定出了一组与发病机制和临床相关的宿主细胞基因，包括TNFRSF10D、CDK2、HSPCA、IL12A，它们是EBV相关的NK/T细胞LPD的共同分子生物学特性，还有一组基因，如PDCD4，被认为是疾病进展的促成因素。本研究从病毒和宿主基因表达方面描述了一种新方法，该方法可识别EBV相关的NK/T细胞LPD中的新型治疗靶点。
