The cutaneous T cell lymphoma, mycosis fungoides, is a human T cell lymphotropic virus-associated disease. A study of 50 patients.

Abstract

For nearly two decades it has been suspected that the cutaneous T cell lymphoma, mycosis fungoides (MF), and its leukemic variant, the Sezary syndrome, are caused by the human T lymphotropic virus (HTLV-I/ll). Arguments against this concept included the finding that only a small number of MF patients have antibodies to HTLV-I/ll and that attempts to detect proviral sequences by mere Southern hybridization of extracted DNA usually met with failure. However, we have reported repeatedly that HTLV-like particles emerge in blood mononuclear cell (PBMC) cultures of practically all patients with this disease. In several instances, the particles were identified as HTLV by immunoelectron microscopy as well as biomolecular analysis. With the assumptions that the virus in MF patients may have become defective and that the remaining signal may be too weak for detection by Southern hybridization alone, the extracts of freshly isolated PBMC of 50 consecutive patients were subjected to combined PCR/Southern analysis. Here we report the presence of HTLV pol and/or tax proviral sequences in 46 out of 50 (92%) of the patients tested. In addition, five of the patients, who lacked antibodies to HTLV-I/ll structural proteins, were found to be seropositive for tax. It thus seems reasonable to conclude that MF/ Sezary syndrome is an HTLV-associated disease and that lack of an immune response does not preclude infection with this type of virus. (J. Clin. Invest. 1995. 95:547-554.)

Mycosis fungoides: is it a Borrelia burgdorferi-associated disease?

“…HTLV-1 is found in adult T-cell lymphoma and leukemia, and it has been implicated by several studies in CTCL (Zucker-Franklin and Pancake, 1994;Pancake et al, 1995;Khan et al, 1996). However, others have not been able to confirm these findings (Boni et al, 1996;Wood et al, 1996).…”

“…Although viruses are known to provide chronic immune stimulation, the findings of their association with MF are controversial (Pancake et al, 1995;Boni et al, 1996;Nagore et al, 2000;Herne et al, 2003). HTLV-1 is found in adult T-cell lymphoma and leukemia, and it has been implicated by several studies in CTCL (Zucker-Franklin and Pancake, 1994;Pancake et al, 1995;Khan et al, 1996).…”

A Human T-Cell Lymphotropic Virus Type 1 Enhancer of Myc Transforming Potential Stabilizes Myc-TIP60 Transcriptional Interactions

“…This cellular background was chosen because ATLL is an aging-related malignancy requiring clinical latency periods of 25 to 40 years prior to disease onset (29), which suggests that genetic mutations linked to the aging process likely contribute to leukemogenesis. Werner's syndrome is a premature aging disorder (45) that mimics or recapitulates many of the clinical and cellular features of normal aging, and WRN locus (8p11-12) mutations have been found in HTLV-1-infected ATLL patient lymphocytes and in HTLV-1-infected mycosis fungoides/Sezary syndrome cells (4,30,53,69,82). Neither c-Myc nor HTLV-1 p30 II (HA) alone significantly induces focus formation in immortalized human WRN Ϫ/Ϫ fibroblasts (Fig.…”

Current views in HTLV-I-associated adult T-cell leukemia/lymphoma

“…Most patients with CTCL are negative for antibodies to the structural proteins of HTLV-I, and thus a causative role for this virus is usually dismissed. However, numerous studies have found HTLV-I-related proviral tax sequence or deleted proviruses in tumor samples from CTCL patients [27][28][29][30][31][32][33][34]. Recently a study on the northeastern coast of Brazil found HTLV-I integrated proviral sequences by southern blot in several mycosis fungoides-like cutaneous lymphomas, and CD30 + largecell anaplastic lymphomas [35].…”