Intervention in Potential Leukemic Cell Migration Pathway Affects Leukemogenesis

  • A. Peled
  • N. Haran-Ghera
Conference paper
Part of the Haematology and Blood Transfusion / Hämatologie und Bluttransfusion book series (HAEMATOLOGY, volume 32)


Several factors are involved in the high frequency of T-cell lymphomas of AKR mice, which appear mainly in the thymus at the age of 6–12 months [1]. The thymus is considered to play a major role in the disease since its removal prevents the development of T-cell lymphoma [2], while retransplantation of thymic epithelium to thymectomized AKR reconstitutes the high frequency of lymphoma [3], Although the AKR/J strain has the predisposition to develop the disease since birth [4], the mean latent period is delayed until the age of 8 months. The long latent period has been attributed to the delayed formation of the leukemogenic dual tropic virus (DTV) with the MCF characteristic [5, 6], formed in the thymus as a consequence of recombination within the envelope gene of ecotropic and xenotropic murine leukemia virus (MuLV). DTVs are detected only in preleukemic thymus and leukemic tissues of strains of mice prone to develop high incidence of leukemia [7]. DTVs enhance leukemia development whereas endogenous ecotropic or xenotropic viruses are usually nontumorigenic. Exceptional is the ecotropic virus isolate SL3 with the enhancing activity on T-cell lymphomagenesis [8]. These observations support the assumption that DTVs are proximal transforming agents of thymocytes and thereby responsible for high incidence of T lymphoma in AKR mice. Cloyd [9] proposed specific cellular tropism of two subclasses of MCF virus, and claimed that oncogenicity is closely linked to cellular differentiation. MCF isolated from lymphomatous thymus was replicating in the thymus and T peripheral cells, while nonlymphomagenic MCF isolated from leukemic spleen of NFS mice did not replicate in the thymus but rather in bone marrow cells, spleen, and lymph node B-lymphocytes.


Murine Leukemia Virus Lymphomatous Thymus Dual Tropic Virus Ecotropic Murine Leukemic Virus Lymphoma Incidence 
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  1. 1.
    Furth J, Seibold HR, Rathbone RR (1933) Experimental studies on lymphomatosis of mice. Am J Cancer 19: 521–527Google Scholar
  2. 2.
    McEndy DP, Boom MB, Furth J (1944) On the role of thymus, spleen and gonads in the development of leukemia in high leukemic strain of mice. Cancer Res 4: 377–383Google Scholar
  3. 3.
    Hays E (1968) The role of thymus epithelial reticular cells in viral leukemiogenesis. Cancer Res 28: 21PubMedGoogle Scholar
  4. 4.
    Rowe WP, Pincus T (1972) Quantitative studies of naturally occurring murine leukemic virus injection of AKR mice. J Exp Med 135: 429–436PubMedCrossRefGoogle Scholar
  5. 5.
    Hartely JW, Walford MK, Old LJ, Rowe WP (1977) A new class of mouse leukemia virus associated with development of spontaneous lymphomas. Proc Natl Acad Sci USA 74: 789–792CrossRefGoogle Scholar
  6. 6.
    Elder JH, Gautsch JW, Jensen FC, Lerner RA, Hartely JW, Row WP (1977) Biochemical evidence that MCF murine leukemic viruses are envelope ( ENV) gene recombinants. Proc Natl Acad Sci USA 74: 4676–4680PubMedCrossRefGoogle Scholar
  7. 7.
    Kawashima K, Ikeda H, Hartley JW, Stockert E, Rowe WP, Old LJ (1976) Changes in expression of murine leukemia virus antigens and production of xenotropic virus in the late preleukemic period in AKR mice. Proc Natl Acad Sci USA 73: 46810–4684CrossRefGoogle Scholar
  8. 8.
    Hays EF, Levy JA (1984) Differences in lymphogenic properties of AKR mouse retroviruses. Virology 138: 49–57PubMedCrossRefGoogle Scholar
  9. 9.
    Cloyd MW (1983) Characterization of target cells for MCF viruses in AKR mice. Cell 32: 217–225PubMedCrossRefGoogle Scholar
  10. 10.
    Haran-Ghera N (1980) Potential leukemic cell among bone marrow of young AKR/J mice. Proc Natl Acad Sci USA 77: 2923–2926PubMedCrossRefGoogle Scholar
  11. 11.
    Haran-Ghera N, Peled A, Hoffman AD, Leef F, Levy JA (1987) Enhanced AKR leukemogenesis by dual tropic viruses. I. The time and site of origin of potential leukemic cells. Leukemia 1: 442–449PubMedGoogle Scholar
  12. 12.
    Buckheit RV Jr, Bolognesi DP, Weinhold KJ (1987) The effects of leukemosuppressive immunotherapy on bone marrow infectious cell centers in AKR mice. Virology 157: 387–396PubMedCrossRefGoogle Scholar
  13. 13.
    Peled A, Haran-Ghera N (1985) High incidence of B cell lymphomas derived from thymectomized AKR mice expressing TL.4 antigen. J Exp Med 162: 1081–1086PubMedCrossRefGoogle Scholar
  14. 14.
    Bedigian HG, Shultz LD, Meier H (1979) Expression of endogenous murine leukemic viruses in AKR/J Strecker mice. Nature 279: 434–436PubMedCrossRefGoogle Scholar
  15. 15.
    Fredrickson TM, Morse HC III, Rowe WP (1984) Spontaneous tumors of NFS mice congenic for ecotropic murine leukemic virus induction loci. J Nat Cancer Inst 73: 521–524PubMedGoogle Scholar
  16. 16.
    Peled A, Haran-Ghera N (1988) Prevention of T cell lymphoma in AKR/J mice. Leukemia 2: 125–131Google Scholar
  17. 17.
    Haran-Ghera N, Trakhtenbrot L, Resnitzky P, Peled A (1989) Preleukemic state in murine leukemogenesis. Leukemia (in press)Google Scholar
  18. 18.
    O’Donnell PV, Nowinski RC, Stockert E (1982) Amplified expression of murine leukemia virus (MuLV)-coded antigens on thymocytes and leukemic cells of AKR mice after infection by dual tropic ( McF) MuLV. Virology 119: 4510–464Google Scholar
  19. 19.
    Scollay R, Bartlett P, Shortman K (1984) T cell development in the adult murine thymus: changes in the expression of the surface antigens Ly-2, L3T4 and B2A2 during development from early precursor cells to migrants. Immunol Rev 82: 79–87PubMedCrossRefGoogle Scholar
  20. 20.
    Stockert E, O’Donnell PV, Ohata Y, Old LJ (1988) Inhibition of AKR leukemogenesis by SMX-1, a dual tropic murine leukemia virus. Proc Natl Acad Sci USA 77: 37210–3724Google Scholar
  21. 21.
    DeRossi A, D’Andrea E, Biasi G, Gollavo D, Chieco-Bianchi L (1983) Protection from spontaneous lymphoma development in SJL/J (v+) mice neonatally injected with dual tropic SJL/151 virus. Proc Natl Acad Sci USA 80: 2775–2779CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1989

Authors and Affiliations

  • A. Peled
    • 1
  • N. Haran-Ghera
    • 1
  1. 1.Department of Chemical ImmunologyThe Weizmann Institute of ScienceRehovotIsrael

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