Gene Expression Profiling of Low-grade B-cell Neoplasms by CGH Analysis

通过 CGH 分析进行低度 B 细胞肿瘤的基因表达谱分析

基本信息

批准号：
13670188
负责人：
KAYANO Hidekazu
金额：
$ 1.86万
依托单位：
Saitama Medical School
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2003
项目状态：
已结题

项目摘要

Indolent B-cell malignancy (IBM) occasionally undergo high-grade transformation (HT), a phenomenon in which IBM cells become larger cells. This research project aimed at profiling of gene expression involved in the HT mechanism of IBM. The following results were yielded.1.In a HT case of splenic marginal zone B-cell lymphoma, a subtype of IBM, we found increased expression of plasmacytic markers such as MUM (multiple myeloma oncogene)1, CD138, and fibroblast growth factor receptor (FGFR)-3 frequently overexpressed by plasmacytoma, as compared with those before HT. It was suggested that the molecular basis of HT was associated with plasmacytic differentiation. Overexpression of FGFR3 was also seen in a case of peripheral T-cell lymphoma. An immunohistochemical study on diffuse large B-cell lymphomas (DLBCL) showed plasmacytom-like co-expression of FGFR3 and CD138 in some cases. Nuclear immunoreactivity of FGFR3 was observed in CD138 -negative DLBCL, suggesting that FGFR3 was phosphorylated, as a tyrosin-kinase, and transferred into nucleus.2.Follicular lymphomas are known to frequently undergo HT. We found that FLs negative for CDlO and/or BCL6 frequently expressed MUM1, and tended to proliferate in a diffuse fashion. Expression patterns of CD10, BCL6, and MUM1 did not change before and after recurrence in some FLs without HT. FL cells however, rarely expressed FGFR3 and CD138. A small-scale study on FL using comparative genomic hybridization (CGH) technique did not show significant difference of chromosomal amplification between MUM1-postive and negative cases.In conclusion, the heterogeneity of molecular basis was suggested in HT of IBM.

懒惰的B细胞恶性肿瘤（IBM）偶尔发生高级转化（HT），这是IBM细胞变成较大细胞的现象。该研究项目旨在分析IBM HT机制中涉及的基因表达。产生了以下结果。1。在HT的脾边缘区B细胞淋巴瘤（IBM的亚型）的HT病例中，我们发现浆细胞标记物（如妈妈（多发性骨髓瘤）1，CD138和成纤维细胞生长因子受体（FGFR）-3经常通过质膜含量过度表达的浆细胞标记的表达增加。有人提出，HT的分子基础与浆细胞分化有关。在外周T细胞淋巴瘤的情况下，还可以看到FGFR3的过表达。一项关于弥漫性大B细胞淋巴瘤（DLBCL）的免疫组织化学研究在某些情况下显示FGFR3和CD138的浆细胞性共表达。在CD138阴性的DLBCL中观察到FGFR3的核免疫反应性，表明FGFR3是磷酸化的，作为酪氨酸激酶，并转移到核中。2.Follicular淋巴瘤已知经常发生HT。我们发现，CDLO和/或BCL6经常表达的MUM1的FL趋于否定，并且倾向于以弥漫性方式增殖。在没有HT的某些FL中，CD10，BCL6和MUM1的表达模式在复发前后没有变化。但是，FL细胞很少表达FGFR3和CD138。使用比较基因组杂交（CGH）技术对FL的一项小规模研究没有显示出MUM1-postive和阴性病例之间的染色体扩增差异。