Analysis of T-cell receptor genes in malignant lymphocytic disease ; Rearrangement of TcR delta chain gene.

恶性淋巴细胞疾病中T细胞受体基因分析；

• 批准号: 63570579
• 负责人: KIMURA Nobuhiro
• 金额: $ 1.28万
• 依托单位: Fukuoka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1988
• 资助国家: 日本
• 起止时间: 1988 至 1989
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-63570579/
• 关键词: TcR delta chain gene; Malignant lymphocytic disease; Gene rearrangement; Hemopoietic tumor; ALL; ATL; T細胞受容体δ鎖遺伝子; 遺伝子解析

We analyzed the rearrangement of T-cell receptor(TcR) delta chain gene, reported as fourth TcR gene, in malignant lymphoproliferative disorders. All of 9 acute lymphoblastic leukemias/lymphoblastic lymphomas(ALL/LBL), of which 4 cases have neither beta nor gamma gene rearrangement, had a new rearranged band of TcR delta locus. Of B-ALL/LBL 41% had rearranged band(s) and of that 23% showed the deletion of TcR delta locus. The VD or DD rearrangement in B-lineage and DD, DJ or VDJ in T- lineage ALL/LBL are suggested due to the results of the delta gene rearrangement pattern. The frequency of the new rearranged band(s) and deletion of the delta locus was 10% and 40% in T-lymphomas, 7% and 9% in B-lymphomas, 20% and 40% in AILDs, and 7% and 7% in acute myelocytic leukemias(AML). Any cases with Hodgkin's disease and adult T-cell leukemia/lymphoma(ATL/ATLL) did not have a new rearranged band of delta locus. The frequency of the delta deletion in those diseases were 61% and 83%. It is suggested that ATL/ATLL, T-lymphoma and a part of Hodgkin's disease and AILD are originated from alpha beta-T-cell. Appearance of delta rearranged band in B-lymphoma and AML are suggested as a missprogram of those tumor cells. The analysis of delta chain gene in T-cell lines show that there is pre-alpha beta T-cell subclass in alpha beta T-lineage.Finally, these studies suggest that 1) the delta chain gene rearranges at a very early stage of the T-cell differentiation, prior to the other TcR genes. 2) delta gene analysis is an useful tool to evaluate clonality, particularly for the most immature T-cell leukemia/lymphoma with no lineage-associated markers or rearrangement of the other TcR genes. 3) rearrangement of TcR delta is not lineage specific but useful in evaluating lymphold lineage of ALL/LBL, when used in conjunction with the immunoglobulin heavy chain gene.

我们分析了T细胞受体（TcR）δ链基因重排，报告的第四TcR基因，在恶性淋巴组织增生性疾病。9例急性淋巴细胞白血病/淋巴母细胞淋巴瘤（ALL/LBL）TcR δ基因重排均出现一条新的重排带，其中4例既无β基因重排，也无γ基因重排。在B-ALL/LBL中，41%有重排带，其中23%有TcR δ位点缺失。根据δ基因重排模式的结果，提出B系可能存在VD或DD重排，T系可能存在DD、DJ或VDJ重排。新重排条带和δ位点缺失的频率在T淋巴瘤中为10%和40%，在B淋巴瘤中为7%和9%，在AILD中为20%和40%，在急性髓细胞白血病（AML）中为7%和7%。任何霍奇金病和成人T细胞白血病/淋巴瘤（ATL/ATLL）病例均未出现新的δ基因重排带。δ缺失率分别为61%和83%。提示ATL/ATLL、T淋巴瘤、部分霍奇金病和AILD均起源于α β T细胞。在B淋巴瘤和AML中出现δ重排带，提示这两种肿瘤细胞可能存在错配。对T细胞系δ链基因的分析表明，在α β T细胞系中存在前α β T细胞亚群，并提示：（1）δ链基因在T细胞分化的早期就发生重排，先于其它TcR基因; 2)δ基因分析是评估克隆性的有用工具，特别是对于没有谱系相关标记或其他TcR基因重排的最不成熟T细胞白血病/淋巴瘤。3)TcR δ重排不是谱系特异性的，但当与免疫球蛋白重链基因结合使用时，可用于评估ALL/LBL的淋巴细胞谱系。

项目成果

木村暢宏 その他: "分子遺伝学的な高悪性度リンパ腫の診断ー危険因子としての二重遺伝子型とMaltiple再構成バンド" 日本綱内系学会雑誌. 29. 321-327 (1989)

Nobuhiro Kimura 等：“高级别淋巴瘤的分子遗传学诊断 - 双基因型和多重重排带作为危险因素”日本内科学会杂志 29. 321-327 (1989)。

N. Kimura et al.: "Diagnosis of high risk lymphoma by molecular genotypic analysis ; Bigenotype and multiple rearranged bands as risk factor." J Jpn Soc R.E.S. 29(4):321-327, 1989.

N. Kimura 等人：“通过分子基因型分析诊断高危淋巴瘤；双基因型和多个重排带作为危险因素。”

木村暢宏、他: "分子遺伝学的な高悪性度リンパ腫の診断ー急険因子としての二重遺伝子型とMultiple再構成バンド" 日本網内系学会雑誌. 29. 321-327 (1989)

Nobuhiro Kimura 等人：“高级别淋巴瘤的分子遗传学诊断 - 双基因型和多重重排带作为危险因素”日本网状内皮系统学会杂志 29. 321-327 (1989)。

Nobuhiro Kimura et al.: "Rearrangement of T-cell receptor δ chain gene as marker of lineage and clonality in T cell lymphoproliferative disorders." Cancer Research. 49. 4488-4492 (1989)

Nobuhiro Kimura 等人：“T 细胞受体 δ 链基因的重排作为 T 细胞淋巴增殖性疾病的谱系和克隆性标记。”49. 4488-4492 (1989)。

N. Uike et al.: "Dual rearrangement of immunoglobulin and T-cell receptor genes in blast crisis of CML." Eur J Haematol 42:460-465, 1989.

N. Uike 等人：“CML 急变期免疫球蛋白和 T 细胞受体基因的双重重排。”