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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1986 Jun;83(12):4524–4528. doi: 10.1073/pnas.83.12.4524

Adult T-cell leukemia/lymphoma not associated with human T-cell leukemia virus type I.

M Shimoyama, Y Kagami, K Shimotohno, M Miwa, K Minato, K Tobinai, K Suemasu, T Sugimura
PMCID: PMC323766  PMID: 3012571

Abstract

We describe five patients with adult T-cell leukemia/lymphoma (ATL) with neither integration of human T-cell leukemia virus type I (HTLV-I) into their leukemia cells nor anti-HTLV-I antibody in their sera. These findings indicate that HTLV-I may not have been involved in leukemogenesis in these patients. The clinicohematological, cytopathological, and immunological features of HTLV-I-negative ATL were exactly the same as those of HTLV-I-associated ATL. Leukemia cells with pleomorphic nuclei, generalized lymphadenopathy, hepatosplenomegaly, skin lesions, hypercalcemia, and elevated lactate dehydrogenase levels, all of which are characteristic features of typical ATL, were also seen in these patients with HTLV-I-negative ATL. Leukemia cells expressed T3, T4, and pan-T-cell antigens in three cases, and T3 and pan-T-cell antigens in two. All five patients had lived in ATL-nonendemic areas. The finding of HTLV-I-negative ATL suggests that factor(s) other than HTLV-I infection may be involved in ATL leukemogenesis.

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Selected References

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  1. Blattner W. A., Kalyanaraman V. S., Robert-Guroff M., Lister T. A., Galton D. A., Sarin P. S., Crawford M. H., Catovsky D., Greaves M., Gallo R. C. The human type-C retrovirus, HTLV, in Blacks from the Caribbean region, and relationship to adult T-cell leukemia/lymphoma. Int J Cancer. 1982 Sep 15;30(3):257–264. doi: 10.1002/ijc.2910300302. [DOI] [PubMed] [Google Scholar]
  2. Catovsky D., Greaves M. F., Rose M., Galton D. A., Goolden A. W., McCluskey D. R., White J. M., Lampert I., Bourikas G., Ireland R. Adult T-cell lymphoma-leukaemia in Blacks from the West Indies. Lancet. 1982 Mar 20;1(8273):639–643. doi: 10.1016/s0140-6736(82)92200-0. [DOI] [PubMed] [Google Scholar]
  3. Catovsky D., Matutes E., Moss V., Brito-Babapulle V. T-cell leukaemias with "helper" phenotype in adults. Lancet. 1985 Oct 26;2(8461):945–946. doi: 10.1016/s0140-6736(85)90875-x. [DOI] [PubMed] [Google Scholar]
  4. Fujisawa J., Seiki M., Kiyokawa T., Yoshida M. Functional activation of the long terminal repeat of human T-cell leukemia virus type I by a trans-acting factor. Proc Natl Acad Sci U S A. 1985 Apr;82(8):2277–2281. doi: 10.1073/pnas.82.8.2277. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Haseltine W. A., Sodroski J., Patarca R., Briggs D., Perkins D., Wong-Staal F. Structure of 3' terminal region of type II human T lymphotropic virus: evidence for new coding region. Science. 1984 Jul 27;225(4660):419–421. doi: 10.1126/science.6330894. [DOI] [PubMed] [Google Scholar]
  6. Hinuma Y., Nagata K., Hanaoka M., Nakai M., Matsumoto T., Kinoshita K. I., Shirakawa S., Miyoshi I. Adult T-cell leukemia: antigen in an ATL cell line and detection of antibodies to the antigen in human sera. Proc Natl Acad Sci U S A. 1981 Oct;78(10):6476–6480. doi: 10.1073/pnas.78.10.6476. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Hoshino H., Esumi H., Miwa M., Shimoyama M., Minato K., Tobinai K., Hirose M., Watanabe S., Inada N., Kinoshita K. Establishment and characterization of 10 cell lines derived from patients with adult T-cell leukemia. Proc Natl Acad Sci U S A. 1983 Oct;80(19):6061–6065. doi: 10.1073/pnas.80.19.6061. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Kalyanaraman V. S., Sarngadharan M. G., Nakao Y., Ito Y., Aoki T., Gallo R. C. Natural antibodies to the structural core protein (p24) of the human T-cell leukemia (lymphoma) retrovirus found in sera of leukemia patients in Japan. Proc Natl Acad Sci U S A. 1982 Mar;79(5):1653–1657. doi: 10.1073/pnas.79.5.1653. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Kitamura T., Takano M., Hoshino H., Shimotohno K., Shimoyama M., Miwa M., Takaku F., Sugimura T. Methylation pattern of human T-cell leukemia virus in vivo and in vitro: pX and LTR regions are hypomethylated in vivo. Int J Cancer. 1985 May 15;35(5):629–635. doi: 10.1002/ijc.2910350510. [DOI] [PubMed] [Google Scholar]
  10. McKelvey E. M., Gottlieb J. A., Wilson H. E., Haut A., Talley R. W., Stephens R., Lane M., Gamble J. F., Jones S. E., Grozea P. N. Hydroxyldaunomycin (Adriamycin) combination chemotherapy in malignant lymphoma. Cancer. 1976 Oct;38(4):1484–1493. doi: 10.1002/1097-0142(197610)38:4<1484::aid-cncr2820380407>3.0.co;2-i. [DOI] [PubMed] [Google Scholar]
  11. Pandolfi F., Manzari V., De Rossi G., Semenzato G., Lauria F., Liso V., Ranucci A., Pizzolo G., Barillari G., Aiuti F. T-helper phenotype chronic lymphocytic leukaemia and "adult T-cell leukaemia" in Italy. Endemic HTLV-I-related T-cell leukaemias in southern Europe. Lancet. 1985 Sep 21;2(8456):633–636. doi: 10.1016/s0140-6736(85)90004-2. [DOI] [PubMed] [Google Scholar]
  12. Seiki M., Eddy R., Shows T. B., Yoshida M. Nonspecific integration of the HTLV provirus genome into adult T-cell leukaemia cells. Nature. 1984 Jun 14;309(5969):640–642. doi: 10.1038/309640a0. [DOI] [PubMed] [Google Scholar]
  13. Seiki M., Hattori S., Hirayama Y., Yoshida M. Human adult T-cell leukemia virus: complete nucleotide sequence of the provirus genome integrated in leukemia cell DNA. Proc Natl Acad Sci U S A. 1983 Jun;80(12):3618–3622. doi: 10.1073/pnas.80.12.3618. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Shimoyama M., Minato K., Tobinai K., Nagai M., Setoya T., Takenaka T., Ishihara K., Watanabe S., Hoshino H., Miwa M. Atypical adult T-cell leukemia-lymphoma: diverse clinical manifestations of adult T-cell leukemia-lymphoma. Jpn J Clin Oncol. 1983;13 (Suppl 2):165–187. [PubMed] [Google Scholar]
  15. Shimoyama M., Minato K., Tobinai K., Nagai M., Setoya T., Watanabe S., Hoshino H., Miwa M., Nagoshi H., Ichiki N. Anti-ATLA (antibody to adult T-cell leukemia-lymphoma virus-associated antigen)-negative adult T-cell leukemia-lymphoma. Jpn J Clin Oncol. 1983;13 (Suppl 2):245–256. [PubMed] [Google Scholar]
  16. Sodroski J. G., Rosen C. A., Haseltine W. A. Trans-acting transcriptional activation of the long terminal repeat of human T lymphotropic viruses in infected cells. Science. 1984 Jul 27;225(4660):381–385. doi: 10.1126/science.6330891. [DOI] [PubMed] [Google Scholar]
  17. Tanaka Y., Koyanagi Y., Chosa T., Yamamoto N., Hinuma Y. Monoclonal antibody reactive with both p28 and p19 of adult T-cell leukemia virus-specific polypeptides. Gan. 1983 Jun;74(3):327–330. [PubMed] [Google Scholar]
  18. Uchiyama T., Yodoi J., Sagawa K., Takatsuki K., Uchino H. Adult T-cell leukemia: clinical and hematologic features of 16 cases. Blood. 1977 Sep;50(3):481–492. [PubMed] [Google Scholar]
  19. Yamada Y., Kamihira S., Amagasaki T., Kinoshita K., Kusano M., Ikeda S., Toriya K., Suzuyama J., Ichimaru M. Changes of adult T cell leukemia cell surface antigens at relapse or at exacerbation phase after chemotherapy defined by use of monoclonal antibodies. Blood. 1984 Aug;64(2):440–444. [PubMed] [Google Scholar]
  20. Yamaguchi K., Nishimura H., Kohrogi H., Jono M., Miyamoto Y., Takatsuki K. A proposal for smoldering adult T-cell leukemia: a clinicopathologic study of five cases. Blood. 1983 Oct;62(4):758–766. [PubMed] [Google Scholar]
  21. Yamaguchi K., Seiki M., Yoshida M., Nishimura H., Kawano F., Takatsuki K. The detection of human T cell leukemia virus proviral DNA and its application for classification and diagnosis of T cell malignancy. Blood. 1984 May;63(5):1235–1240. [PubMed] [Google Scholar]
  22. Yoshida M., Seiki M., Yamaguchi K., Takatsuki K. Monoclonal integration of human T-cell leukemia provirus in all primary tumors of adult T-cell leukemia suggests causative role of human T-cell leukemia virus in the disease. Proc Natl Acad Sci U S A. 1984 Apr;81(8):2534–2537. doi: 10.1073/pnas.81.8.2534. [DOI] [PMC free article] [PubMed] [Google Scholar]

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