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PRDM1/BLIMP-1在多种B细胞和T细胞淋巴瘤中的表达

PRDM1/BLIMP-1 expression in multiple B and T-cell lymphoma.

作者信息

Garcia José-Francisco, Roncador Giovanna, García Juan-Fernando, Sánz Ana-Isabel, Maestre Lorena, Lucas Elena, Montes-Moreno Santiago, Fernandez Victoria Rebeca, Martinez-Torrecuadrara Jorge L, Marafioti Teresa, Mason David Y, Piris Miguel A

机构信息

Monoclonal Antibodies Unit, Biotechnology Program, Spanish National Cancer Centre (CNIO), Madrid, Spain.

出版信息

Haematologica. 2006 Apr;91(4):467-74.

Abstract

BACKGROUND AND OBJECTIVES

The positive regulatory domain I (PRDM1) protein or BLIMP-1, belonging to the PRDM gene family of transcriptional repressors, is a key regulator of terminal differentiation in B-lymphocytes and is critical for plasma cell differentiation.

DESIGN AND METHODS

Here we document the expression of PRDM1 in normal and neoplastic lymphoid cells, through the use of a monoclonal antibody that recognizes the molecule in paraffin-embedded tissue sections. A large series of B and T-cell lymphomas (679 cases) was studied, using tissue microarrays.

RESULTS

Multiple myeloma, plasmacytoma and lymphoplasmacytic lymphoma cases (n=19) were positive. Plasmablastic lymphoma, oral mucosa-type (n=15), were also found to be positive. PRDM1 protein was expressed in some cases of B-cell neoplasia, i.e. chronic lymphocytic leukemia/small lymphocytic lymphoma (15%), diffuse large B-cell lymphoma (43%), classical Hodgkin's lymphoma (41%) and also in T-cell lymphoma (23%).

INTERPRETATION AND CONCLUSIONS

Most B-neoplastic cells showing plasmablastic differentiation were PRDM1-positive. Unexpectedly, a subset of diffuse large B-cell lymphoma expressed PRDM1, lacked detectable plasmablastic or immunoblastic changes and displayed more aggressive behavior, with a shorter failure-free survival. In contrast to normal B-cells, diffuse large B-cell lymphoma cases with increased PRDM1 expression co-expressed BCL-6 and MUM1/IRF4, confirming that PRDM1 expression in these tumors is insufficient to drive the full genetic program associated with plasmacytic differentiation.

摘要

背景与目的

阳性调控结构域I(PRDM1)蛋白即B淋巴细胞诱导成熟蛋白-1(BLIMP-1),属于转录抑制因子的PRDM基因家族,是B淋巴细胞终末分化的关键调节因子,对浆细胞分化至关重要。

设计与方法

在此,我们通过使用一种能识别石蜡包埋组织切片中该分子的单克隆抗体,记录PRDM1在正常和肿瘤性淋巴细胞中的表达情况。利用组织芯片研究了一系列大量的B细胞和T细胞淋巴瘤(679例)。

结果

多发性骨髓瘤、浆细胞瘤和淋巴浆细胞性淋巴瘤病例(n = 19)呈阳性。口腔黏膜型浆母细胞性淋巴瘤(n = 15)也呈阳性。PRDM1蛋白在一些B细胞肿瘤病例中表达,即慢性淋巴细胞白血病/小淋巴细胞淋巴瘤(15%)、弥漫性大B细胞淋巴瘤(43%)、经典型霍奇金淋巴瘤(41%),在T细胞淋巴瘤中也有表达(23%)。

解读与结论

大多数显示浆母细胞分化的B肿瘤细胞PRDM1呈阳性。出乎意料的是,一部分弥漫性大B细胞淋巴瘤表达PRDM1,缺乏可检测到的浆母细胞或免疫母细胞改变,且表现出更具侵袭性的行为,无病生存期更短。与正常B细胞相反,PRDM1表达增加的弥漫性大B细胞淋巴瘤病例共表达BCL-6和MUM1/IRF4,证实这些肿瘤中PRDM1的表达不足以驱动与浆细胞分化相关的完整基因程序。

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