Rearrangements of Genes for the Antigen Receptor on T Cells as Markers of Lineage and Clonality in Human Lymphoid Neoplasms

Abstract

The Tα and Tβ 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 Tβ gene as a widely applicable marker of clonality in the T-cell lineage. We show that the Tβ 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—predominant 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. (N Engl J Med 1985; 313:776–83.)