Waldmann T A, Davis M M, Bongiovanni K F, Korsmeyer S J
N Engl J Med. 1985 Sep 26;313(13):776-83. doi: 10.1056/NEJM198509263131303.
The T alpha and T beta chains of the heterodimeric T-lymphocyte antigen receptor are encoded by separated DNA segments that recombine during T-cell development. We have used rearrangements of the T beta gene as a widely applicable marker of clonality in the T-cell lineage. We show that the T beta genes are used in both the T8 and T4 subpopulations of normal T cells and that Sézary leukemia, adult T-cell leukemia, and the non-B-lineage acute lymphoblastic leukemias are clonal expansions of T cells. Furthermore, circulating T cells from a patient with the T8-cell-predominantly lymphocytosis associated with granulocytopenia are shown to be monoclonal. Finally, the sensitivity and specificity of this tumor-associated marker have been exploited to monitor the therapy of a patient with adult T-cell leukemia. These unique DNA rearrangements provide insights into the cellular origin, clonality, and natural history of T-cell neoplasia.
异二聚体T淋巴细胞抗原受体的Tα和Tβ链由在T细胞发育过程中发生重排的分开的DNA片段编码。我们已将Tβ基因的重排用作T细胞谱系中广泛适用的克隆性标志物。我们发现,Tβ基因在正常T细胞的T8和T4亚群中均有使用,并且Sezary白血病、成人T细胞白血病以及非B系急性淋巴细胞白血病都是T细胞的克隆性扩增。此外,一名患有与粒细胞减少相关的以T8细胞为主的淋巴细胞增多症患者的循环T细胞被证明是单克隆的。最后,这种肿瘤相关标志物的敏感性和特异性已被用于监测一名成人T细胞白血病患者的治疗。这些独特的DNA重排为T细胞肿瘤形成的细胞起源、克隆性和自然史提供了见解。