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SCID Mice as a Model for Human Leukemias

  • Alessandra Cesano
  • Daniela Santoli
Chapter
Part of the Medical Intelligence Unit book series (MIU.LANDES)

Abstract

The murine severe combined immunodeficiency (SCID) mutation, first reported in 1983 by Bosma and coworkers,1 affects a component of the recombinase system used in common by T and B lymphocytes to assemble the genes that code for the variable regions of antigen receptors.2–4 As a result, SCID mice are severely deficient in T-cell receptor (TCR)- and immunoglobulin receptor (IgR)-bearing lymphocytes, lack serum Ig, do not respond to immunologic in vitro assays testing for B- or T-cell function, and histopathologically, show severe lymphopenia in all lymphoid tissues.1 Despite the impairment in Band T-lymphocyte differentiation, SCID mice have normal natural killer (NK) cell function, and their hematopoietic microenvironment is intact as it contains normally functioning antigen-presenting cells and is able to promote the differentiation of normal stem cells into functionally competent T and B lymphocytes.1,5–7 Because of these characteristics, SCID mice have been excellent models for the propagation of human xenografts, superior to and more convenient than regular or splenectomized nude mice. The recognition that SCID mice are able to support the growth of human cells has led to a blooming of literature on the construction of SCID mouse-human chimeras. While the usefulness of the SCID mouse for studying murine and human hematopoiesis is addressed in other sections of this book, this chapter deals exclusively with the engraftment of human leukemias in this model system. Prior to the discovery of SCID mice, transfer of primary patient leukemia cells or established leukemic cell lines into nude mice had resulted in either engraftment failure, or in some cases, in the production of myelosarcomas, localized solid tumors, or ascites, all of which do not reflect the normal course of the disease in humans.8–16

Keywords

U937 Cell Acute Myelogenous Leukemia SCID Mouse Human Leukemia Severe Combine Immunodeficiency 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Bosma GC, Custer RP, Bosma MJ. A severe combined immunodeficiency mutation in the mouse. Nature 1983; 301: 527–30.PubMedCrossRefGoogle Scholar
  2. 2.
    Schuler W, Weiler IJ, Schuler A et al. Rearrangement of antigen receptor genes is defective in mice with severe combined immune deficiency. Cell 1986; 46: 963–72.PubMedCrossRefGoogle Scholar
  3. 3.
    Malynn BA, Blackwell TK, Fulop GM et al. The SCID defect affects the final step of immunoglobulin VDJ recombinase mechanism. Cell 1988; 54: 453–60.PubMedCrossRefGoogle Scholar
  4. 4.
    Lieber MR, Hesse JE, Lewis S et al. The defect of murine severe combined immune deficiency: joining of signal sequences but not coding segments in V(D)J recombination. Cell 1988; 55: 7–16.PubMedCrossRefGoogle Scholar
  5. 5.
    Dorshkind K, Keller GM, Phillips RA et al. Functional status of cells from lymphoid and myeloid tissues in mice with severe combined immunodeficiency disease. J Immunol 1984; 132: 1804–8.PubMedGoogle Scholar
  6. 6.
    Czitrom AA, Edwards S, Phillips RA et al. The function of antigen-presenting cells in mice with severe combined immunodeficiency. J Immunol 1985; 134: 2276–80.PubMedGoogle Scholar
  7. 7.
    Zinkernagel RM, Ruedi E, Althage A et al. Thymic selection of H-2–incompatible bone marrow cells in SCID mice. J Exp Med 1988; 168: 1187–92.PubMedCrossRefGoogle Scholar
  8. 8.
    Franks CR, Bishop D, Balkwill FR et al. Growth of acute myeloid leukemia as discrete subcutaneous tumors in immune-deprived mice. Br J Cancer 1977; 35: 697–700.PubMedCrossRefGoogle Scholar
  9. 9.
    Lozzio BB, Machado EA, Lozzio CB et al. Hereditary asplenic-athymic mice: transplantation of human myelogenous leukemic cells. J Exp Med 1976; 143: 225–31.PubMedCrossRefGoogle Scholar
  10. 10.
    Machado EA, Gerard DA, Lozzio CB et al. Proliferation and differentiation of human myeloid leukemic cells in immunodeficient mice: electron microscopy and cytochemistry. Blood 1984; 63: 1015–22.PubMedGoogle Scholar
  11. 11.
    Lozzio BB, Lozzio CB, Machado E. Human myelogenous (Ph+) leukemic cell line: transplantation into athymic mice. J Natl Cancer Inst 1976; 56: 627–9.PubMedGoogle Scholar
  12. 12.
    Nilsson K, Giovanella BC, Stehlin JS et al. Tumorigenicity of human hematopoietic cell line in athymic nude mice. Int J Cancer 1977; 19: 337–44.PubMedCrossRefGoogle Scholar
  13. 13.
    Watanabe S, Shimosato Y, Kuroki M et al. Transplantability of human lymphoid cell line, lymphoma and leukemia in splenectomized and/or irradiated nude mice. Cancer Res 1980; 40: 2588–95.PubMedGoogle Scholar
  14. 14.
    Ghose T, Lee CLY, Faulkner G et al. Progression of a human B cell chronic lymphocytic leukemia line in nude mice. Am J Hematol 1988; 28: 146–54.PubMedCrossRefGoogle Scholar
  15. 15.
    Machado EA, Lozzio BB, Lozzio CB et al. Development of myelosarcomas from human myelogenous leukemia cells transplanted in athymic mice. Cancer Res 1977; 37: 3995–4002.PubMedGoogle Scholar
  16. 16.
    Clutterbuck RD, Mills CA, Moey P et al. Studies on the development of acute myeloid-leukemia xenografts in immune-deprived mice: comparison with cells in short-term culture. Leuk Res 1985; 9: 1511–8.PubMedCrossRefGoogle Scholar
  17. 17.
    Cesano A, O’Connor R, Lange B et al. Homing and progression patterns of childhood acute lymphoblastic leukemias in severe combined immunodeficiency mice. Blood 1991; 77: 2463–74.PubMedGoogle Scholar
  18. 18.
    Cesano A, Hoxie JA, Lange B et al. The severe combined immunodeficient (SCID) mouse as a model for human myeloid leukemias. Oncogene 1992; 7: 827–36.PubMedGoogle Scholar
  19. 19.
    Cesano A, O’Connor R, Nowell PC et al. Establishment of a karyotypically normal cytotoxic leukemic T-cell line from a T-ALL sample engrafted in SCID mice. Blood 1993; 81: 2714–22.PubMedGoogle Scholar
  20. 20.
    Hendrickson EA. The SCID mouse: relevance as an animal model system for studying human disease. Am J Pathol 1993; 143: 1511–22.PubMedGoogle Scholar
  21. 21.
    O’Connor R, Cesano A, Lange B et al. Growth factor requirements of childhood acute-T-lymphoblastic leukemia: correlation between presence of chromosomal abnormalities and ability to grow permanently in vitro. Blood 1991; 77: 1534–45.PubMedGoogle Scholar
  22. 22.
    Erikson J, Finger L, Sun L et al. Deregulation of c-myc by translocation of the a locus of the T-cell receptor in leukemias. Science 1986; 232: 884–6.PubMedCrossRefGoogle Scholar
  23. 23.
    Champagne E, Takihara U, Sagman U et al. The T-cell receptor delta chain locus is disrupted in the T-ALL associated t(11;14)(p13–;q11) translocation. Blood 1989; 73: 1672–6.PubMedGoogle Scholar
  24. 24.
    Kamel-Reid S, Letarte M, Sirard C et al. A model of human acute lymphoblastic leukemia in immune-deficient SCID mice. Science 1989; 246: 1597–1600.PubMedCrossRefGoogle Scholar
  25. 25.
    Kamel-Reid S, Letarte M, Doedens M et al. Bone marrow from children in relapse with pre-B acute lymphoblastic leukemia proliferates and disseminates rapidly in seid mice. Blood 1991; 78: 2973–81.PubMedGoogle Scholar
  26. 26.
    Jansen B, Vallera DA, Laszcz WB et al. Successful treatment of human acute T-cell leukemia in SCID mice using the anti-CD7–deglycosylated ricin A-chain immunotoxin DA7. Cancer Res 1992; 52: 1314–21.PubMedGoogle Scholar
  27. 27.
    Uckun FM, Manivel C, Arthur D et al. In vivo efficacy of B43 (anti-CD 19)-pokeweed antiviral protein immunotoxin against human pre-B cell acute lymphoblastic leukemia in mice with severe combined immunodeficiency. Blood 1992; 79: 2201–14.PubMedGoogle Scholar
  28. 28.
    Jansen B, Uckun FM, Jaszcz WB et al. Establishment of a human t(4;11) leukemia in severe combined immunodeficient mice and successfull treatment using anti-CD19 (B43)-pokeweed antiviral protein immunotoxin. Cancer Res 1992; 52: 406–12.PubMedGoogle Scholar
  29. 29.
    Gunther R, Chelstrom LM, Finnegan D et al. In vivo anti-leukemic efficacy of anti-CD7–pokeweed antiviral protein immunotoxin against human T-lineage acute lymphoblastic leukemia/lymphoma in mice with severe combined immunodeficiency. Leukemia 1993; 7: 298–309.PubMedGoogle Scholar
  30. 30.
    Jansen B, Kersey JH, Jaszcz WB et al. Effective immunotherapy of human t(4;11) leukemia in mice with severe combined immunodeficiency (SCID) using B43 (anti-CD19)-pokeweed antiviral protein immunotoxin plus cyclophosphamide. Leukemia 1993; 7: 290–7.PubMedGoogle Scholar
  31. 31.
    Shah SA, Halloran PM, Ferris CA et al. Anti-B4–blocked ricin immunotoxin shows therapeutic efficacy in four different SCID mouse tumor models. Cancer Res 1993; 53: 1360–7.PubMedGoogle Scholar
  32. 32.
    Uckun FM, Myers DE, Irvin JD et al. Effects of the intermolecular toxin-monoclonal antibody linkage on the in vivo stability, immunogenicity and anti-leukemic activity of B43 (anti-CD19) pokeweed antiviral protein immunotoxin. Leuk Lymphoma 1993; 9: 459–76.PubMedCrossRefGoogle Scholar
  33. 33.
    McCulloch E. Stem cells in normal and leukemic hemopoiesis (Henry Stratten Lecture). Blood 1983; 62: 1–8.PubMedGoogle Scholar
  34. 34.
    Avanzi GC, Brizzi MF, Giannotti J et al. M-07e human leukemic factor-dependent cell line provides a rapid and sensitive bioassay for the human cytokines GM-CSF and IL-3. J Cell Physiol 1990; 145: 458–64.PubMedCrossRefGoogle Scholar
  35. 35.
    Lange B, Valtieri M, Santoli D et al. Growth factor requirements of childhood acute leukemia: establishment of GM-CSF-dependent cell lines. Blood 1987; 70: 192–9.PubMedGoogle Scholar
  36. 36.
    Santoli D, O’Connor R, Cesano A et al. Synergistic and antagonistic effects of and IL-4, respectively, on the IL-2 dependent growth of a T-cell receptor-yb human T leukemia cell line. J Immunol 1990; 144: 4703–11.PubMedGoogle Scholar
  37. 37.
    Cesano A, Visonneau S, Cioe L et al. Reversal of acute myelogenous leukemia in humanized SCID mice using a novel adoptive transfer approach. J Clin Invest 1994, in press.Google Scholar
  38. 38.
    Sawyers C, Gishizky M, Quan S et al. Propagation of human blastic myeloid leukemia in the seid mouse. Blood 1992; 79: 2089–98.PubMedGoogle Scholar
  39. 39.
    Lapidot T, Pflumio F, Dick JE. Modeling human hematopoiesis in immunodeficient mice. Lab Anim Sci 1993; 43: 147–50.PubMedGoogle Scholar
  40. 40.
    Namikawa R, Ueda R, Kyoizumi S. Growth of human myeloid leukemias in the human marrow environment of SCID-hu mice. Blood 1993; 82: 2526–36.PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1995

Authors and Affiliations

  • Alessandra Cesano
  • Daniela Santoli

There are no affiliations available

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