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. 1995 Feb 14;92(4):1057–1061. doi: 10.1073/pnas.92.4.1057

Development of leukemia in mice transgenic for the tax gene of human T-cell leukemia virus type I.

W J Grossman 1, J T Kimata 1, F H Wong 1, M Zutter 1, T J Ley 1, L Ratner 1
PMCID: PMC42636  PMID: 7862633

Abstract

The human T-cell leukemia virus type I Tax protein trans-activates several cellular genes implicated in T-cell replication and activation. To investigate its leukemogenic potential, Tax was targeted to the mature T-lymphocyte compartment in transgenic mice by using the human granzyme B promoter. These mice developed large granular lymphocytic leukemia, demonstrating that expression of Tax in the lymphocyte compartment is sufficient for the development of leukemia. Furthermore, these observations suggest that human T-cell leukemia virus infection may be involved in the development of large granular lymphocytic leukemia.

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Selected References

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

  1. Ballard D. W., Böhnlein E., Lowenthal J. W., Wano Y., Franza B. R., Greene W. C. HTLV-I tax induces cellular proteins that activate the kappa B element in the IL-2 receptor alpha gene. Science. 1988 Sep 23;241(4873):1652–1655. doi: 10.1126/science.241.4873.1652. [DOI] [PubMed] [Google Scholar]
  2. Benvenisty N., Ornitz D. M., Bennett G. L., Sahagan B. G., Kuo A., Cardiff R. D., Leder P. Brain tumours and lymphomas in transgenic mice that carry HTLV-I LTR/c-myc and Ig/tax genes. Oncogene. 1992 Dec;7(12):2399–2405. [PubMed] [Google Scholar]
  3. Burton R. C., Koo G. C., Smart Y. C., Clark D. A., Winn H. J. Surface antigens of murine natural killer cells. Int Rev Cytol. 1988;111:185–210. doi: 10.1016/s0074-7696(08)61734-9. [DOI] [PubMed] [Google Scholar]
  4. Chan W. C., Gu L. B., Masih A., Nicholson J., Vogler W. R., Yu G., Nasr S. Large granular lymphocyte proliferation with the natural killer-cell phenotype. Am J Clin Pathol. 1992 Mar;97(3):353–358. doi: 10.1093/ajcp/97.3.353. [DOI] [PubMed] [Google Scholar]
  5. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  6. Dokhelar M. C., Pickford H., Sodroski J., Haseltine W. A. HTLV-I p27rex regulates gag and env protein expression. J Acquir Immune Defic Syndr. 1989;2(5):431–440. [PubMed] [Google Scholar]
  7. Fujii M., Sassone-Corsi P., Verma I. M. c-fos promoter trans-activation by the tax1 protein of human T-cell leukemia virus type I. Proc Natl Acad Sci U S A. 1988 Nov;85(22):8526–8530. doi: 10.1073/pnas.85.22.8526. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Furuta Y., Aizawa S., Suda Y., Ikawa Y., Kishimoto H., Asano Y., Tada T., Hikikoshi A., Yoshida M., Seiki M. Thymic atrophy characteristic in transgenic mice that harbor pX genes of human T-cell leukemia virus type I. J Virol. 1989 Jul;63(7):3185–3189. doi: 10.1128/jvi.63.7.3185-3189.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Gessain A., Barin F., Vernant J. C., Gout O., Maurs L., Calender A., de Thé G. Antibodies to human T-lymphotropic virus type-I in patients with tropical spastic paraparesis. Lancet. 1985 Aug 24;2(8452):407–410. doi: 10.1016/s0140-6736(85)92734-5. [DOI] [PubMed] [Google Scholar]
  10. Green J. E., Begley C. G., Wagner D. K., Waldmann T. A., Jay G. trans activation of granulocyte-macrophage colony-stimulating factor and the interleukin-2 receptor in transgenic mice carrying the human T-lymphotropic virus type 1 tax gene. Mol Cell Biol. 1989 Nov;9(11):4731–4737. doi: 10.1128/mcb.9.11.4731. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hanson R. D., Sclar G. M., Kanagawa O., Ley T. J. The 5'-flanking region of the human CGL-1/granzyme B gene targets expression of a reporter gene to activated T-lymphocytes in transgenic mice. J Biol Chem. 1991 Dec 25;266(36):24433–24438. [PubMed] [Google Scholar]
  12. Heneine W., Khabbaz R. F., Lal R. B., Kaplan J. E. Sensitive and specific polymerase chain reaction assays for diagnosis of human T-cell lymphotropic virus type I (HTLV-I) and HTLV-II infections in HTLV-I/II-seropositive individuals. J Clin Microbiol. 1992 Jun;30(6):1605–1607. doi: 10.1128/jcm.30.6.1605-1607.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Heusel J. W., Hanson R. D., Silverman G. A., Ley T. J. Structure and expression of a cluster of human hematopoietic serine protease genes found on chromosome 14q11.2. J Biol Chem. 1991 Apr 5;266(10):6152–6158. [PubMed] [Google Scholar]
  14. Hinrichs S. H., Nerenberg M., Reynolds R. K., Khoury G., Jay G. A transgenic mouse model for human neurofibromatosis. Science. 1987 Sep 11;237(4820):1340–1343. doi: 10.1126/science.2888191. [DOI] [PubMed] [Google Scholar]
  15. Iwakura Y., Tosu M., Yoshida E., Takiguchi M., Sato K., Kitajima I., Nishioka K., Yamamoto K., Takeda T., Hatanaka M. Induction of inflammatory arthropathy resembling rheumatoid arthritis in mice transgenic for HTLV-I. Science. 1991 Aug 30;253(5023):1026–1028. doi: 10.1126/science.1887217. [DOI] [PubMed] [Google Scholar]
  16. Kimata J. T., Ratner L. Temporal regulation of viral and cellular gene expression during human T-lymphotropic virus type I-mediated lymphocyte immortalization. J Virol. 1991 Aug;65(8):4398–4407. doi: 10.1128/jvi.65.8.4398-4407.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Korber B., Okayama A., Donnelly R., Tachibana N., Essex M. Polymerase chain reaction analysis of defective human T-cell leukemia virus type I proviral genomes in leukemic cells of patients with adult T-cell leukemia. J Virol. 1991 Oct;65(10):5471–5476. doi: 10.1128/jvi.65.10.5471-5476.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Levitt L. J., Reyes G. R., Moonka D. K., Bensch K., Miller R. A., Engleman E. G. Human T cell leukemia virus-I-associated T-suppressor cell inhibition of erythropoiesis in a patient with pure red cell aplasia and chronic T gamma-lymphoproliferative disease. J Clin Invest. 1988 Feb;81(2):538–548. doi: 10.1172/JCI113352. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Lo K. M., Vivier E., Rochet N., Dehni G., Levine H., Haseltine W. A., Anderson P. Infection of human natural killer (NK) cells with replication-defective human T cell leukemia virus type I provirus. Increased proliferative capacity and prolonged survival of functionally competent NK cells. J Immunol. 1992 Dec 15;149(12):4101–4108. [PubMed] [Google Scholar]
  20. Loughran T. P., Jr Clonal diseases of large granular lymphocytes. Blood. 1993 Jul 1;82(1):1–14. [PubMed] [Google Scholar]
  21. Loughran T. P., Jr, Coyle T., Sherman M. P., Starkebaum G., Ehrlich G. D., Ruscetti F. W., Poiesz B. J. Detection of human T-cell leukemia/lymphoma virus, type II, in a patient with large granular lymphocyte leukemia. Blood. 1992 Sep 1;80(5):1116–1119. [PubMed] [Google Scholar]
  22. Martin M. P., Biggar R. J., Hamlin-Green G., Staal S., Mann D. Large granular lymphocytosis in a patient infected with HTLV-II. AIDS Res Hum Retroviruses. 1993 Aug;9(8):715–719. doi: 10.1089/aid.1993.9.715. [DOI] [PubMed] [Google Scholar]
  23. Metcalf D., Begley C. G., Williamson D. J., Nice E. C., De Lamarter J., Mermod J. J., Thatcher D., Schmidt A. Hemopoietic responses in mice injected with purified recombinant murine GM-CSF. Exp Hematol. 1987 Jan;15(1):1–9. [PubMed] [Google Scholar]
  24. Nerenberg M., Hinrichs S. H., Reynolds R. K., Khoury G., Jay G. The tat gene of human T-lymphotropic virus type 1 induces mesenchymal tumors in transgenic mice. Science. 1987 Sep 11;237(4820):1324–1329. doi: 10.1126/science.2888190. [DOI] [PubMed] [Google Scholar]
  25. Ohshima K., Kikuchi M., Masuda Y., Kobari S., Sumiyoshi Y., Eguchi F., Mohtai H., Yoshida T., Takeshita M., Kimura N. Defective provirus form of human T-cell leukemia virus type I in adult T-cell leukemia/lymphoma: clinicopathological features. Cancer Res. 1991 Sep 1;51(17):4639–4642. [PubMed] [Google Scholar]
  26. Ratner L. Regulation of expression of the c-sis proto-oncogene. Nucleic Acids Res. 1989 Jun 12;17(11):4101–4115. doi: 10.1093/nar/17.11.4101. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Ratner L. Regulation of expression of the c-sis proto-oncogene. Nucleic Acids Res. 1989 Jun 12;17(11):4101–4115. doi: 10.1093/nar/17.11.4101. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. 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]
  29. Wano Y., Hattori T., Matsuoka M., Takatsuki K., Chua A. O., Gubler U., Greene W. C. Interleukin 1 gene expression in adult T cell leukemia. J Clin Invest. 1987 Sep;80(3):911–916. doi: 10.1172/JCI113152. [DOI] [PMC free article] [PubMed] [Google Scholar]

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