Skip to main content
PMC home page
The American Journal of Pathology logoLink to The American Journal of Pathology
. 1997 Feb;150(2):667–673.

No evidence of HTLV-I proviral integration in lymphoproliferative disorders associated with cutaneous T-cell lymphoma.

G S Wood 1, J M Schaffer 1, R Boni 1, R Dummer 1, G Burg 1, M Takeshita 1, M Kikuchi 1
PMCID: PMC1858284  PMID: 9033279

Abstract

Several recent studies have reported detection of HTLV-I genetic sequences in patients with cutaneous T-cell lymphoma (CTCL) including mycosis fungoides and Sezary syndrome. The purpose of this study was to determine whether HTLV-I was detectable in lesional tissues of patients suffering from diseases known to be associated with CTCL. Thirty-five cases were obtained from diverse geographical locations including Ohio, California, Switzerland, and Japan. Six of them had concurrent CTCL. Cases were analyzed using a combination of genomic polymerase chain reaction (PCR)/ Southern blot, dot blot, and Southern blot analyses. All assays were specific for HTLV-I provirus. Sensitivity ranged from approximately 10(-6) for PCR-based studies to 10(-2) for unamplified genomic blotting. Lesional DNA from patients with lymphomatoid papulosis (fourteen cases), Hodgkin's disease (twelve cases), and CD30+ large-cell lymphoma (nine cases) was tested for the HTLV-I proviral pX region using a genomic PCR assay followed by confirmatory Southern blot analysis with a nested oligonucleotide pX probe. All cases were uniformly negative. All of the Hodgkin's disease cases, eight of the large-cell lymphoma cases, and six of the lymphomatoid papulosis cases were then subjected to dot blot analysis of genomic DNA using a full-length HTLV-I proviral DNA probe that spans all regions of the HTLV-I genome. Again, all cases were negative. Finally, eleven of the Hodgkin's disease cases were also subjected to Southern blot analysis of EcoRI-digested genomic DNA using the same full-length HTLV-I probe. Once again, all cases were negative. These findings indicated that, despite utilization of a variety of sensitive and specific molecular biological methods, HTLV-I genetic sequences were not detectable in patients with CTCL-associated lymphoproliferative disorders. These results strongly suggest that the HTLV-I retrovirus is not involved in the pathogenesis of these diseases.

Full text

PDF
667

Images in this article

670Figure 1
on p.670
670Figure 2
on p.670
670Figure 3
on p.670
670Figure 4
on p.670
671Figure 5
on p.671

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Anagnostopoulos I., Hummel M., Kaudewitz P., Herbst H., Braun-Falco O., Stein H. Detection of HTLV-I proviral sequences in CD30-positive large cell cutaneous T-cell lymphomas. Am J Pathol. 1990 Dec;137(6):1317–1322. [PMC free article] [PubMed] [Google Scholar]
  2. Davis T. H., Morton C. C., Miller-Cassman R., Balk S. P., Kadin M. E. Hodgkin's disease, lymphomatoid papulosis, and cutaneous T-cell lymphoma derived from a common T-cell clone. N Engl J Med. 1992 Apr 23;326(17):1115–1122. doi: 10.1056/NEJM199204233261704. [DOI] [PubMed] [Google Scholar]
  3. Detmar M., Pauli G., Anagnostopoulos I., Wunderlich U., Herbst H., Garbe C., Stein H., Orfanos C. E. A case of classical mycosis fungoides associated with human T-cell lymphotropic virus type I. Br J Dermatol. 1991 Feb;124(2):198–202. doi: 10.1111/j.1365-2133.1991.tb00434.x. [DOI] [PubMed] [Google Scholar]
  4. Hall W. W., Liu C. R., Schneewind O., Takahashi H., Kaplan M. H., Röupe G., Vahlne A. Deleted HTLV-I provirus in blood and cutaneous lesions of patients with mycosis fungoides. Science. 1991 Jul 19;253(5017):317–320. doi: 10.1126/science.1857968. [DOI] [PubMed] [Google Scholar]
  5. Hall W. W. Response. Science. 1993 Mar 5;259(5100):1471–1471. doi: 10.1126/science.259.5100.1471. [DOI] [PubMed] [Google Scholar]
  6. Kaudewitz P., Herbst H., Anagnostopoulos I., Eckert F., Braun-Falco O., Stein H. Lymphomatoid papulosis followed by large-cell lymphoma: immunophenotypical and genotypical analysis. Br J Dermatol. 1991 May;124(5):465–469. doi: 10.1111/j.1365-2133.1991.tb00627.x. [DOI] [PubMed] [Google Scholar]
  7. Lee S. H., Su I. J., Chen R. L., Lin K. S., Lin D. T., Chuu W. M., Lin K. S. A pathologic study of childhood lymphoma in Taiwan with special reference to peripheral T-cell lymphoma and the association with Epstein-Barr viral infection. Cancer. 1991 Nov 1;68(9):1954–1962. doi: 10.1002/1097-0142(19911101)68:9<1954::aid-cncr2820680918>3.0.co;2-e. [DOI] [PubMed] [Google Scholar]
  8. Manzari V., Gismondi A., Barillari G., Morrone S., Modesti A., Albonici L., De Marchis L., Fazio V., Gradilone A., Zani M. HTLV-V: a new human retrovirus isolated in a Tac-negative T cell lymphoma/leukemia. Science. 1987 Dec 11;238(4833):1581–1583. doi: 10.1126/science.2825353. [DOI] [PubMed] [Google Scholar]
  9. Pancake B. A., Zucker-Franklin D., Coutavas E. E. The cutaneous T cell lymphoma, mycosis fungoides, is a human T cell lymphotropic virus-associated disease. A study of 50 patients. J Clin Invest. 1995 Feb;95(2):547–554. doi: 10.1172/JCI117697. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Srivastava B. I., Banki K., Perl A. Human T-cell leukemia virus type I or a related retrovirus in patients with mycosis fungoides/Sézary syndrome and Kaposi's sarcoma. Cancer Res. 1992 Aug 15;52(16):4391–4395. [PubMed] [Google Scholar]
  11. Takeshita M., Ohshima K., Akamatsu M., Ohgami A., Kikuchi M., Suzumiya J., Uike N., Okamura T., Nakayama J. CD30-positive anaplastic large cell lymphoma in a human T-cell lymphotropic virus-I endemic area. Hum Pathol. 1995 Jun;26(6):614–619. doi: 10.1016/0046-8177(95)90165-5. [DOI] [PubMed] [Google Scholar]
  12. Whittaker S. J., Luzzatto L. HTLV-1 provirus and mycosis fungoides. Science. 1993 Mar 5;259(5100):1470–1471. doi: 10.1126/science.8451645. [DOI] [PubMed] [Google Scholar]
  13. Wood G. S., Bahler D. W., Hoppe R. T., Warnke R. A., Sklar J. L., Levy R. Transformation of mycosis fungoides: T-cell receptor beta gene analysis demonstrates a common clonal origin for plaque-type mycosis fungoides and CD30+ large-cell lymphoma. J Invest Dermatol. 1993 Sep;101(3):296–300. doi: 10.1111/1523-1747.ep12365416. [DOI] [PubMed] [Google Scholar]
  14. Wood G. S., Crooks C. F., Uluer A. Z. Lymphomatoid papulosis and associated cutaneous lymphoproliferative disorders exhibit a common clonal origin. J Invest Dermatol. 1995 Jul;105(1):51–55. doi: 10.1111/1523-1747.ep12312548. [DOI] [PubMed] [Google Scholar]
  15. Wood G. S., Hardman D. L., Boni R., Dummer R., Kim Y. H., Smoller B. R., Takeshita M., Kikuchi M., Burg G. Lack of the t(2;5) or other mutations resulting in expression of anaplastic lymphoma kinase catalytic domain in CD30+ primary cutaneous lymphoproliferative disorders and Hodgkin's disease. Blood. 1996 Sep 1;88(5):1765–1770. [PubMed] [Google Scholar]
  16. Zhao L. J., Giam C. Z. Interaction of the human T-cell lymphotrophic virus type I (HTLV-I) transcriptional activator Tax with cellular factors that bind specifically to the 21-base-pair repeats in the HTLV-I enhancer. Proc Natl Acad Sci U S A. 1991 Dec 15;88(24):11445–11449. doi: 10.1073/pnas.88.24.11445. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Zucker-Franklin D., Coutavas E. E., Rush M. G., Zouzias D. C. Detection of human T-lymphotropic virus-like particles in cultures of peripheral blood lymphocytes from patients with mycosis fungoides. Proc Natl Acad Sci U S A. 1991 Sep 1;88(17):7630–7634. doi: 10.1073/pnas.88.17.7630. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The American Journal of Pathology are provided here courtesy of American Society for Investigative Pathology

RESOURCES