The gene expression profile of nodal peripheral T-cell lymphoma demonstrates a molecular link between angioimmunoblastic T-cell lymphoma (AITL) and follicular helper T (TFH) cells
The gene expression profile of nodal peripheral T-cell lymphoma demonstrates a molecular link between angioimmunoblastic T-cell lymphoma (AITL) and follicular helper T (TFH) cells
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DOI：
10.1182/blood-2006-10-055145
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发表时间：
2007-06-01
期刊：
影响因子：
20.3
通讯作者：
Gaulard, Philippe
中科院分区：
文献类型：
--
作者：
de Leval, Laurence;Rickman, David S.;Gaulard, Philippe
血管免疫母细胞性T细胞淋巴瘤（AITL）和外周T细胞淋巴瘤非特指型（PTCL - u）发病机制的分子改变在很大程度上是未知的。为了描述这两种疾病实体之间的个体发生和分子差异，使用基因表达谱分析了一系列AITL（n = 18）和PTCL - u（n = 16）。无监督聚类与病理分类以及PTCL - u中的CD30表达相关。AITL的分子特征表现为强烈的微环境印记（B细胞和滤泡树突状细胞相关基因、趋化因子以及细胞外基质和血管生物学相关基因的过表达），以及几种正常滤泡辅助性T（T - FH）细胞特征性基因（CXCL13、BCL6、PDCD1、CD40L、NFATC1）的过表达。通过基因集富集分析，AITL的分子特征在已发表的T - FH特异性基因中显著富集。分选的AITL细胞比组织样本的富集程度更高。通过免疫组化在AITL中验证了几种T - FH基因的过表达。在CD30（-）PTCL - u中鉴定出少数具有分子T - FH样特征的病例。我们的研究结果有力地支持了TFH细胞是AITL的正常对应细胞，并表明AITL的谱系可能比预期的更广泛，因为一部分CD30（-）PTCL - u可能源自AITL或与AITL相关。
The molecular alterations underlying the pathogenesis of angioimmunoblastic T-cell lymphoma (AITL) and peripheral T-cell lymphoma, unspecified (PTCL-u) are largely unknown. In order to characterize the ontogeny and molecular differences between both entities, a series of AITLs (n = 18) and PTCLs-u (n = 16) was analyzed using gene expression profiling. Unsupervised clustering correlated with the pathological classification and with CD30 expression in PTCL-u. The molecular profile of AITLs was characterized by a strong microenvironment imprint (overexpression of B-cell- and follicular dendritic cell-related genes, chemokines, and genes related to extracellular matrix and vascular biology), and overexpression of several genes characteristic of normal follicular helper T (T-FH) cells (CXCL13, BCL6, PDCD1, CD40L, NFATC1). By gene set enrichment analysis, the AITL molecular signature was significantly enriched in published T-FH-specific genes. The enrichment was higher for sorted AITL cells than for tissue samples. Overexpression of several T-FH genes was validated by immunohistochemistry in AITLs. A few cases with molecular T-FH-like features were identified among CD30(-) PTCLs-u. Our findings strongly support that TFH cells represent the normal counterpart of AITL, and suggest that the AITL spectrum may be wider than suspected, as a subset of CD30(-) PTCLs-u may derive from or be related to AITL.