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外周T细胞淋巴瘤(非特指型)和弥漫性大B细胞淋巴瘤的转录本分析确定了不同的肿瘤特征性标记。

Transcript profiling in peripheral T-cell lymphoma, not otherwise specified, and diffuse large B-cell lymphoma identifies distinct tumor profile signatures.

作者信息

Mahadevan Daruka, Spier Catherine, Della Croce Kimiko, Miller Susan, George Benjamin, Riley Chris, Warner Stephen, Grogan Thomas M, Miller Thomas P

机构信息

Department of Medicine, Arizona Cancer Center, University of Arizona, 1515 North Campbell Avenue, Tucson, AZ 85724, USA.

出版信息

Mol Cancer Ther. 2005 Dec;4(12):1867-79. doi: 10.1158/1535-7163.MCT-05-0146.

Abstract

To glean biological differences and similarities of peripheral T-cell lymphoma-not otherwise specified [PTCL-NOS] to diffuse large B-cell lymphoma (DLBCL), a transcriptosome analysis was done on five PTCL-NOS and four DLBCL patients and validated by quantitative real-time reverse transcription-PCR on 10 selected genes. Normal peripheral blood T cells, peripheral blood B cells, and lymph node were used as controls. The resultant gene expression profile delineated distinct "tumor profile signatures" for PTCL-NOS and DLBCL. Several highly overexpressed genes in both PTCL-NOS and DLBCL involve the immune network, stroma, angiogenesis, and cell survival cascades that make important contributions to lymphomagenesis. Inflammatory chemokines and their receptors likely play a central role in these complex interrelated pathways: CCL2 and CXCR4 in PTCL-NOS and CCL5 and CCR1 in DLBCL. Highly overexpressed oncogenes unique to PTCL-NOS are SPI1, STK6, alpha-PDGFR, and SH2D1A, whereas in DLBCL they are PIM1, PIM2, LYN, BCL2A1, and RAB13. Oncogenes common to both lymphomas are MAFB, MET, NF-kappaB2, LCK, and LYN. Several tumor suppressors are also down-regulated (TPTE, MGC154, PTCH, ST5, and SUI1). This study illustrates the relevance of tumor-stroma immune trafficking and identified potential novel prognostic markers and targets for therapeutic intervention.

摘要

为了探究外周T细胞淋巴瘤,非特指型[PTCL-NOS]与弥漫性大B细胞淋巴瘤(DLBCL)之间的生物学差异和相似性,对5例PTCL-NOS患者和4例DLBCL患者进行了转录组分析,并通过对10个选定基因进行定量实时逆转录PCR验证。正常外周血T细胞、外周血B细胞和淋巴结用作对照。所得基因表达谱描绘了PTCL-NOS和DLBCL独特的“肿瘤谱特征”。PTCL-NOS和DLBCL中几个高度过表达的基因涉及免疫网络、基质、血管生成和细胞存活级联反应,这些对淋巴瘤的发生起着重要作用。炎症趋化因子及其受体可能在这些复杂的相互关联途径中起核心作用:PTCL-NOS中的CCL2和CXCR4以及DLBCL中的CCL5和CCR1。PTCL-NOS特有的高度过表达的癌基因是SPI1、STK6、α-PDGFR和SH2D1A,而在DLBCL中是PIM1、PIM2、LYN、BCL2A1和RAB13。两种淋巴瘤共有的癌基因是MAFB、MET、NF-κB2、LCK和LYN。几种肿瘤抑制因子也下调(TPTE、MGC154、PTCH、ST5和SUI1)。本研究阐明了肿瘤-基质免疫运输的相关性,并确定了潜在的新型预后标志物和治疗干预靶点。

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