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The role of HTLV-I tax in T cell lymphomasNYU Medical Center, Dept of Medicine, New York, NYIn regions of the world where the human lymphotropic virus Type I (HTLV-I) is not endemic, this virus is rarely considered to play a role in the development of lymphoid neoplasms or autoimmune diseases. Even, if it is considered, this etiology is readily dismissed, if the patient in question proves to be serologically negative for antibodies to the structural proteins of HTLV-I/II. Yet, it is known, that the transactivating, transforming sequence of HTLV-I and the protein it encodes - Tax and p40Tax respectively, may be the cause of the afore mentioned diseases, even when the DNA sequences encoding the structural proteins of the virus have been deleted. This phenomenon has been well recognized in Japan. Pursuant to the discovery, that practically all patients with the cutaneous T cell lymphoma (CTCL), mycosis fungoides carry HTLV-I tax in their skin infiltrating and peripheral blood lymphocytes, and that they have antibodies to p40Tax (1-4), we learned, that 8% of healthy New York City blood donors, are also HTLV-I tax positive, even though they have no antibodies to HTLV-I/II, when this is tested by western blot (5,6). Moreover, Tax can be transmitted to rabbits by transfusion of Tax-positive human lymphocytes (7). In addition, it was shown, that upwards of 24% of patients with rheumatoid arthritis or lupus erythematosus carry the Tax sequence in their mononuclear cells (8,9). These observations have several implications: (a) Transmission of HTLV-I Tax by transfusion or by breast feeding of Tax-positive lymphocytes could be prevented, and (b) The development of a new treatment modality, namely, antisense oligonucleotides targeted specifically against Tax, may be considered as a new treatment modality for Tax-positive lymphomas. References: (1) Sem Dermatol 1994;13:160. (2) J Clin Invest. 1995;95:547. (3) Blood 1996;88:3004. (4) J Invest Dermatol 1996;106:667. (5) Lancet 1997; 349: (6) Clin Diagnostic Lab Immunol 1998;5:831, 1998 (7) Clin Diagn Lab Immunol 2000;77:274. (8) Clin Exp Rheumatol 2001; in press. (9) Zucker-Franklin D. The role of human T cell lymphotropic virus Type I Tax in the development of cutaneous T cell lymphoma In: Cutaneous T cell lymphoma: Basic and clinically relevant biology. Edelson R, DeVita VT, eds. Ann New York Acad Sci 2001; 941:86-96. For more information, contact zucked01@mcmbox.med.nyu.edu Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Viral Oncogenesis. |
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