T-cell/natural killer (T/NK)-cell lymphomas represent a group of poor-risk lymphoproliferative disorders that have only recently been recognized as distinct clinicopathologic entities. The average outcome with currently available therapy is substantially inferior to that of aggressive B-cell lymphomas. Significant gaps remain in our knowledge of their origin, diagnosis, and clinical spectrum. This review outlines recent developments in the biology and molecular genetics of these disorders, current diagnostic challenges, and future avenues for therapy.
Several cancer-prone transgenic mouse models that develop predominantly T/NK-cell lymphomas have been produced in the past 2 to 3 years. These models point to an important role for chronic cytokine stimulation and for disruption of genes involved in the control of chromatin remodeling and maintenance of genome integrity in the pathogenesis of T-cell lymphomas. The recognition of T/NK-cell lymphomas has been greatly facilitated by the broad acceptance of standard diagnostic criteria and by the increasing availability of assays for the analysis of T-cell receptor rearrangement and a more precise definition of functional T/NK-cell subsets. New drugs with potential for use in T/NK-cell lymphomas, including monoclonal antibodies, tyrosine kinase inhibitors, synthetic retinoids, immunoconjugates, and immunosuppressive molecules with novel mechanisms of action are in the early phase of clinical investigation.
Much remains to be learned in the pathogenesis, clinical spectrum, and optimal therapy of T/NK-cell lymphomas. The availability of animal models of disease, new diagnostic tools, and targeted drugs with novel mechanisms of action should lead to rapid progress in this group of malignancies in the near future.
aDivision of Hematology/Oncology, Department of Medicine; bDivision of Dermatopathology, Department of Pathology; Ohio State University, Columbus, Ohio, USA.
Address correspondence to Pierluigi Porcu, MD, Division of Hematology/Oncology, B-407 Starling Loving Hall, 320 West 10th Avenue, Columbus, OH 43210, USA