T-cell receptor beta chain gene rearrangements: genetic markers of T-cell lineage and clonality.

T-cell receptor beta chain gene rearrangements: genetic markers of T-cell lineage and clonality.
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T 细胞受体 β 链基因重排:T 细胞谱系和克隆性的遗传标记。

DOI:
10.1016/s0046-8177(86)80125-3
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发表时间:
1986
期刊:
影响因子:
3.3
通讯作者:
Dalla-Favera,R
Dalla-Favera,R
中科院分区:
医学3区
文献类型:
--
作者:
Knowles2nd,DM;Pelicci,PG;Dalla-Favera,R

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我们已经进行了一系列的调查,涉及T细胞受体β链(T β)基因重排在良性和恶性非造血,B细胞和T细胞增殖。这些研究为使用T β基因重排作为T细胞谱系、克隆性和分化的标志物提供了概念基础和操作方法,类似于B细胞中的免疫球蛋白基因重排。现在可以利用针对T β基因重排的Southern印迹杂交分析来鉴定和区分非T细胞、多克隆T细胞和单克隆T细胞。T β基因重排的检测将在T细胞肿瘤的进一步研究和分类中发挥重要作用。然而,T细胞克隆性遗传标记的鉴定也具有重要的诊断和预后价值。例如,确定特定恶性T细胞克隆特有的T β基因重排为该克隆T细胞增殖提供了特异性遗传标记。T细胞克隆的这种遗传标记可能为监测患者的治疗反应和复发的早期迹象的临床过程提供有用的工具。尽管如此,我们的研究表明,免疫球蛋白和T β基因重排的谱系特异性不是绝对的。似乎只有一个多参数的方法相结合的广泛的单克隆抗体免疫表型分析,在体外测试功能的帮助和抑制,和Southern印迹杂交分析免疫球蛋白和T β基因重排允许的结论性和明确的证据的B细胞或T细胞来源的所有淋巴肿瘤。在这种广泛的多参数分析后,不能被分配到B或T细胞谱系的类肉瘤恶性肿瘤是非常罕见的。
We have performed a series of investigations involving T-cell receptor beta chain (T beta) gene rearrangements in benign and malignant nonhematopoietic, B-cell, and T-cell proliferations. These studies provide the conceptual basis and the operational approach for the use of T beta gene rearrangements as markers of T-cell lineage, clonality, and differentiation, analogous to immunoglobulin gene rearrangements in B cells. Southern blot hybridization analysis for T beta gene rearrangements can now be utilized to identify and distinguish between non-T cells, polyclonal T cells, and monoclonal T cells. Determination of T beta gene rearrangements will play an important role in the further investigation and classification of T-cell neoplasia. However, the identification of a genetic marker of clonality for T cells has significant diagnostic and prognostic value as well. For example, determination of the T beta gene rearrangement unique to a particular malignant T-cell clone provides a specific genetic marker for that clonal T-cell proliferation. This genetic marker of the T-cell clone may provide a useful tool for monitoring the patient's therapeutic response and clinical course for early signs of relapse. Nonetheless, our studies demonstrate that the lineage specificity of immunoglobulin and T beta gene rearrangements is not absolute. It appears that only a multiparametric approach combining extensive monoclonal antibody immunophenotypic analysis, in vitro testing for functional help and suppression, and Southern blot hybridization analysis for immunoglobulin and T beta gene rearrangements allows the conclusive and unequivocal demonstration of the B-or T-cell derivation of all lymphoid neoplasms. Lymphoid malignancies that cannot be assigned to the B-or T-cell lineage following this extensive multiparametric analysis are exceedingly uncommon.