Knowles D M, Pelicci P G, Dalla-Favera R
Hum Pathol. 1986 Jun;17(6):546-51. doi: 10.1016/s0046-8177(86)80125-3.
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.
我们进行了一系列研究，涉及良性和恶性非造血性、B细胞及T细胞增殖中的T细胞受体β链（Tβ）基因重排。这些研究为将Tβ基因重排用作T细胞谱系、克隆性及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，针对Tβ基因重排的Southern印迹杂交分析可用于识别和区分非T细胞、多克隆T细胞及单克隆T细胞。Tβ基因重排的测定在T细胞肿瘤的进一步研究和分类中将发挥重要作用。然而，T细胞克隆性遗传标志物的鉴定也具有显著的诊断和预后价值。例如，特定恶性T细胞克隆特有的Tβ基因重排的测定为该克隆性T细胞增殖提供了一种特异性遗传标志物。这种T细胞克隆的遗传标志物可能为监测患者的治疗反应及临床病程以发现复发早期迹象提供有用工具。尽管如此，我们的研究表明免疫球蛋白和Tβ基因重排的谱系特异性并非绝对。似乎只有一种多参数方法，将广泛的单克隆抗体免疫表型分析、功能性辅助和抑制的体外检测以及免疫球蛋白和Tβ基因重排的Southern印迹杂交分析相结合，才能确凿无疑地证明所有淋巴样肿瘤的B细胞或T细胞来源。经过这种广泛的多参数分析后仍无法归为B细胞或T细胞谱系的淋巴样恶性肿瘤极为罕见。
