Chromosome translocation junction genes on lympho-hematopoietic cell proliferation and differentiation
Chromosome translocation junction genes on lympho-hematopoietic cell proliferation and differentiation
批准号:
11470215
负责人:
SETO Masao
金额:
$9.34万
依托单位:
依托单位国家:
日本
项目类别:
Grant-in-Aid for Scientific Research (B)
财政年份:
1999
资助国家:
日本
项目状态:
已结题
起止时间:
1999 至 2001
中文摘要
我们报道了染色体18q21上的一个新基因MALT1,该基因参与粘膜相关淋巴组织(MALT)淋巴瘤t(11;18)(q21;q21)。这种易位导致API2在11q21位点和MALT1在18q21位点融合,产生API2-MALT1嵌合产物。我们目前正在尝试生产针对API2和MALT1产物的单克隆抗体,以便我们可以用免疫组织化学方法检查MALT淋巴瘤病例。我们研究了弥漫性大B细胞淋巴瘤(DLBCL),已知它包含几个亚型,尽管在不同的血液病理学家中很难获得亚型分类的共识。我们检测了BCL1、BCL2、BCL6基因重排及免疫染色。我们发现细胞表面标记物可以作为描述临床显著亚型的标记物。事实上,我们发现CD5+ DLBCL组成了一组预后不良的患者,其预后与套细胞淋巴瘤一样差。易位连接基因与t细胞淋巴瘤的关系尚不清楚。基于已有报道t细胞淋巴瘤在6q21位点有频繁的染色体畸变,我们试图分离相关基因。我们在t细胞淋巴母细胞样淋巴瘤细胞系HT-1和成人t细胞白血病/淋巴瘤细胞系ATM-1中发现了一个新的TCBA1基因。TCBA1在淋巴瘤中的作用目前正在研究中。
英文摘要
We have reported a novel gene MALT1 at chromosome 18q21 that is involved in mucosa-associated lymphoid tissue (MALT) lymphoma t(11;18)(q21;q21). This translocation results in fusion between API2 at 11q21 and MALT1 at 18q21, producing API2-MALT1 chimeric products. We are now trying to produce monoclonal antibodies against API2 and MALT1 products so that we can examine MALT lymphoma cases with immunohistochemial method.We have studied diffuse large B cell lymphoma(DLBCL) that was known to contain several subtypes although consensus for subtype classifications is difficult to obtain among various hematopathologists. We have examined BCL1, BCL2, BCL6 gene rearrangement as well as immunostaining. We found that cell surface markers could serve as markers depicting clinically significant subtypes. Indeed, CD5+ DLBCL was found to consist of a group with poor prognosis which is as worse as mantle cell lymphoma.Translocation junction genes that are involved in T-cell lymphoma are poorly understood. Based on the reports that T-cell lymphoma had frequent chromosome aberration at 6q21, we attempted to isolate the responsible genes. We identified a novel TCBA1 gene that is altered in T-cell lymphoblastoid lymphoma cell line HT-1 and adult T-cell leukemia/lymphoma cell line ATM-1. The role of TCBA1 for lymphomageneis is now under investigation.
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Inagaki, h., Okabe, M., Seto, M., Nakamura, s., Ueda, R., Eimoto, T.: "API2-MALT1 fusion transcripts involved in mucosa-associated lymphoid tissue lymphoma : multiplex RT-PCR detection using formalin -fixed paraffin embedded specimens"Am J Pathol.. 158. 6
Inagaki, h.、Okabe, M.、Seto, M.、Nakamura, s.、Ueda, R.、Eimoto, T.:“参与粘膜相关淋巴组织淋巴瘤的 API2-MALT1 融合转录本:多重 RT-PCR 检测
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Sugiyama, T., Saka, K., Nakamura, S., Yonezumi, s., Seto, M.: "API2-MALT1 chimeric transcipt is a predictive marker for the responsive ess of H. pylori eradication reatment in low-grade gastric MALT lymphoma"Gastroenterology. 120. 884-1889 (2001)
Sugiyama, T.、Saka, K.、Nakamura, S.、Yonezumi, s.、Seto, M.:“API2-MALT1 嵌合转录物是低级别胃幽门螺杆菌根除治疗反应性的预测标志物
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Eguchi, M., Eguchi, M., Seto, M., Morishita, K., Suzuki, K., ueda, R., Ueda, K., amada, N., Graeaves, M.: "GPHN, A novel partner gene fused to MLL in a leukemia itht(11;14)(q23;q24)"Genes, Chromosomes Cancer. 32. 212-221 (2001)
江口,M.,江口,M.,濑户,M.,森下,K.,铃木,K.,上田,R.,上田,K.,阿田,N.,格雷夫斯,M.:“GPHN,一部小说
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Lucas, P. 他: "Bcl10 and MALT1, independent targets of chromosomal translocation in malt lymphoma, cooperate in a novel NF-kappa B signaling pathway"J Biol Chem. 276. 19012-19019 (2001)
Lucas, P. 等人:“Bcl10 和 MALT1,麦芽淋巴瘤中染色体易位的独立靶标,在新的 NF-κ B 信号通路中合作”J Biol Chem. 276. 19012-19019 (2001)
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Nishida, K. 他: "Different susceptibilities of postmitotic checkpoint-proficient and -deficient Balb/3T3 cells to ICRF-193, a catalytic inhibitor of DNA topoisomerase II"Jpn.J.Cancer Res. 92. 193-202 (2001)
Nishida, K. 等人:“有丝分裂后检查点丰富和缺陷的 Balb/3T3 细胞对 ICRF-193(DNA 拓扑异构酶 II 的催化抑制剂)的不同敏感性”Jpn.J.Cancer Res. 92. 193-202 (2001) )
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共 91 条
Lymphomagenesis pathway consisting of various cooperative genes and their relevance as molecular target therapy
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Biological role of genes at genetic alteration regions for proliferation and differentiation in hem
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批准号:18390286
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项目类别:Grant-in-Aid for Scientific Research (B)
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资助金额:$11.23万
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财政年份:2006
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Molecular mechanisms of lymphomagenesis
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项目类别:Grant-in-Aid for Scientific Research on Priority Areas
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资助金额:$54.21万
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财政年份:2005
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负责人:SETO Masao
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Genomic alteration in hematologic malignancies and their roles for proliferation and differentiation
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Roles of translocation junction genes for proliferation and differentiation of hemotolymphoid cell
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项目类别:Grant-in-Aid for Scientific Research (B)
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资助金额:$8.9万
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BIOLOGICAL ROLE OF CHROMOSOME TRANSLOCATION JUNCTION REGION GENES IN HEMATOPOIETIC CELL DIFFERENTIATION AND PROLIFERATION
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