Gene expression profiling of Epstein-Barr virus-positive and -negative monomorphic B-cell posttransplant lymphoproliferative disorders

Gene expression profiling of Epstein-Barr virus-positive and -negative monomorphic B-cell posttransplant lymphoproliferative disorders
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DOI:
10.1097/pdm.0b013e31804f54a9
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发表时间:
2007-09-01
影响因子:
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通讯作者:
Swerdlow, Steven H.
Swerdlow, Steven H.
中科院分区:
其他
文献类型:
--
作者:
Craig, Fiona E.;Johnson, Lawrence R.;Swerdlow, Steven H.

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虽然大多数移植后淋巴组织增生性疾病(PTLD)与EB病毒(EBV)感染有关,但约20%缺乏可检测的EBV(EBV-)。目前尚不确定后者是否真正不同于EBV+ PTLD或可能与另一种感染因子有关。本研究利用基因表达谱分析进一步研究EBV+和EBV-单形性B细胞PTLD之间的关系,并寻找其发病机制的线索。使用Affyestive HU 133 A基因芯片比较4例EBV+和4例EBV -单形B细胞PTLD病例。分层聚类成功区分了EB病毒+和EB病毒-组。相对于EBV-PTLD,54个转录本在EBV + PTLD中过表达。鉴定的转录物包括IRF 7(EBV LMP 1表达的已知调节物)、EBI 2(EBV诱导的基因2)和干扰素诱导的3(MX 1、IFITM 1和IFITM 3)。此外,EBV+组含有232个相对于EBV-组减少的转录物,包括与先前报道的在EBV感染培养的B细胞系后的那些一致的变化。总之,在一小组单形性B细胞PTLD中,EBV +病例显示了与B细胞的EBV感染相关的基因表达变化的子集。相比之下,EBV-PTLD缺乏病毒相关的变化,表明它们在生物学上是不同的。
Although most posttransplant lymphoproliferative disorders (PTLD) are related to Epstein-Barr virus (EBV) infection, approximately 20% lack detectable EBV (EBV-). It is uncertain whether the latter cases are truly distinct from EBV+ PTLD or possibly relate to another infectious agent. This study used gene expression profiling to further investigate the relationship between EBV+ and EBV- monomorphic B-cell PTLD, and to search for clues to their pathogenesis. Affymetrix HU133A GeneChips were used to compare 4 EBV+ and 4 EBV - cases of monomorphic B-cell PTLD. Hierarchical clustering successfully distinguished the EBV+ and EBV - groups. Relative to EBV - PTLD, 54 transcripts were over-expressed in EBV + PTLD. The transcripts identified included IRF7 (a known regulator of EBV LMP1 expression), EBI2 (EBV-induced gene 2), and 3 that are interferon induced (MX1, IFITM1, and IFITM3). In addition, the EBV+ group contained 232 transcripts decreased relative to the EBV- group, including changes concordant with those previously reported after EBV infection of cultured B-cell lines. In summary, in a small group of monomorphic B-cell PTLD, EBV + cases demonstrated a subset of gene expression changes associated with EBV infection of B cells. By contrast, EBV - PTLD lacked viral-associated changes suggesting that they are biologically distinct.