The human T-cell leukemias: clinical, cytomorphologic, immunophenotypic, and genotypic characteristics.

The distribution of the conventional lymphoid cell markers on T lymphocytes and the principal panels of monoclonal antibodies used to recognize distinctive T-lymphocyte-associated differentiation antigens are discussed. These reagents have been used to probe the early and late stages of T-cell differentiation, and a hypothetical schema of T-cell differentiation has been constructed. Application of these reagents to the investigation of neoplastic T cells has resulted in the determination of the subset of origin and the stage of differentiation of the neoplastic cells in T-cell-derived lymphoproliferative malignancies. Recent advances in molecular biology have made possible the Southern blot hybridization analysis of DNA extracted from neoplastic T cells for patterns of T-cell-receptor gene rearrangements. Examination of these patterns in benign and malignant T and non-T cell has provided the basis for the use of T-cell-receptor gene rearrangements as specific genetic markers of T-cell lineage, clonality, and differentiation. These and other advances have resulted in the delineation of a new category of T-cell neoplasia, the adult T-cell leukemia/lymphoma syndrome. They have also demonstrated that the majority of clinically indolent neoplasms composed of large granular lymphocytes in so-called T gamma-lymphoproliferative disease are monoclonal proliferations. Further phenotypic, functional, and genotypic analyses of the T-cell malignancies should provide better understanding of T-lymphocyte differentiation and heterogeneity. Such studies should also lead to better clinicopathologic correlations and greater understanding of the basis for the clinical diversity of the T-cell-derived lymphoproliferative malignancies.