Subtyping of diffuse large B cell lymphomas by molecules highly expressed on germinal center B cells.

根据生发中心 B 细胞高表达的分子对弥漫性大 B 细胞淋巴瘤进行亚型分类。

• 批准号: 13470042
• 负责人: MORI Shigeo
• 金额: $ 7.87万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13470042/
• 关键词: malignant lymphoma; germinal center; bcl-6; methionine aminopeptidase 2; snoRNA; B細胞; pim-1; met-ap2; U50HG

To subdivide the diffuse large B cell lymphoma which is a waste-basket type category in lymphoma differentiation, we intended to add some reliable molecules that contribute in such subdivision. We could identify three molecules that are expressed in diffuse large B cell lymphomas of germinal cents B cell type exclusively : U50HG, methionine aminopeptidase 2 (MetAP2) and cholesterine ester transfer protein (CET). In case of U50HG that is a protein non-coding snoRNA host gene, we found its transcript to be highly expressed in germinal center exclusively. Other two molecules, MetAP2 a CET were detected in germinal center B cells and their neoplastic counterparts intensely by their specific antibodies while very weakly on other B-and T-cell lymphomas. Those results suggest that the three gene products are very much useful for the subdivision of neoplastic B lymphocytes into germinal center type and other (may be activated B cell) type. Furthermore, we found a novel oncogene pim-1 to form a dominant negative type chimeric transcript on a certain B cell lymphoma that exhibit Bc16/Pim1 chromosomal translocation.

为了细分弥漫性大B细胞淋巴瘤，这是淋巴瘤分化中的废纸篓类型类别，我们打算添加一些有助于这种细分的可靠分子。我们可以鉴定出三种仅在生发性B细胞型弥漫性大B细胞淋巴瘤中表达的分子：U 50 HG、甲硫氨酸氨基肽酶2（MetAP 2）和胆固醇酯转移蛋白（CET）。对于非编码蛋白质的snoRNA宿主基因U 50 HG，我们发现其转录本仅在生发中心高表达。另外两种分子MetAP 2 a CET在生殖中心B细胞及其肿瘤对应物中被其特异性抗体强烈检测到，而在其他B细胞和T细胞淋巴瘤中非常弱。这些结果表明，三种基因产物对肿瘤性B淋巴细胞分化为生发中心型和其他（可能是活化的B细胞）型是非常有用的。此外，我们还发现了一个新的癌基因pim-1，在一个具有Bc 16/Pim 1染色体易位的B细胞淋巴瘤中形成显性负型嵌合转录本。

项目成果

Maekawa I, Aoki N, Shiota M, Nojima Y, Mori S: "maintenance and characterization of an Epstein Barr Virus-infected CD56-negative T cell lymphoma."Jpn J Cancer Res. 93. 61-69 (2002)

Maekawa I、Aoki N、Shiota M、Nojima Y、Mori S：“Epstein Barr 病毒感染的 CD56 阴性 T 细胞淋巴瘤的维持和特征。”Jpn J Cancer Res。

Endo H, Takenaga.K, Kanno T, Satoh H, Mori S: "Methionine aminopeptidase 2 is a new target for the metastasis-associated protein, S100A4."J Biol Chem. 277. 26396-26402 (2002)

Endo H、Takenaga.K、Kanno T、Satoh H、Mori S：“蛋氨酸氨肽酶 2 是转移相关蛋白 S100A4 的新靶点。”J Biol Chem。

Nakada C, Tsukamoto Y, Oka A, Nonaka I, Takeda T, Sato K, Mori S, Ito H, Moriyama M: "Cardiac-restricted ankyrin-repeated protein is differentially induced in Duchenne and congenital muscular dystrophy"Lab Invest. 83. 711-719 (2003)

Nakada C、Tsukamoto Y、Oka A、Nonaka I、Takeda T、Sato K、Mori S、Ito H、Moriyama M：“心脏限制性锚蛋白重复蛋白在 Duchenne 和先天性肌营养不良症中差异诱导”Lab Invest。

Kaneita Y, Yoshida S, Ishiguro N, Sawada U, Horie T, Mori S, Moriyama M: "Detection of reciprocal fusion 5'-BCL6 partner-3' transcripts in lymphomas exhibiting reciprocal BCL6 translocations."Brit J Haematol. 113. 803-806 (2001)

Kaneita Y、Yoshida S、Ishiguro N、Sawada U、Horie T、Mori S、Moriyama M：“在表现出相互 BCL6 易位的淋巴瘤中检测相互融合 5-BCL6 伴侣 3 转录本。”Brit J Haematol。

Fujino Y, Mizuno T, Masuda K, Ohno K, Satoh H, Tsujimoto H: "Assignment of the feline Fas (TNFRSF6) gene to chromosome D2p13→p12.2 by fluorescence in situ hybridization."Cytogenet Cell Gene. 95. 122-124 (2001)

Fujino Y、Mizuno T、Masuda K、Ohno K、Satoh H、Tsujimoto H：“通过荧光原位杂交将猫科动物 Fas (TNFRSF6) 基因分配到染色体 D2p13→p12.2。”Cytogenet 细胞基因。 124（2001）