Normal and Leukemic Hematopoiesis in Diffusion Chambers: Comparison with In Vitro Culture Systems

  • H. E. Broxmeyer
  • L. Koltun
  • N. Jacobsen
  • M. A. S. Moore
Conference paper

Abstract

Different assays for progenitor cells of the granulocyte-macrophage lineage were assessed for their capacity to support the proliferation and differentiation of bone marrow and blood cells from patients with leukemia and bone marrow and spleen cells from mice with a transplantable myelomonocytic leukemia originally induced with Graffi’s virus. The heterogeneity of progenitor cell populations revealed by cell separation analysis and culture of cells in semisolid and liquid suspension cultures in vitro and in diffusion chambers implanted into mice was reviewed, as was the responsiveness of these cells to cell-derived inhibitory activities such as lactoferrin, leukemia-associated inhibitory activity (LIA), neutropenia-associated inhibitory activity, and the E-type prostaglandins. Differentiation of cells from patients and mice with leukemia to morphologically mature forms during culture in diffusion chambers but not in the in vitro colony or liquid suspension assays suggests that some of the factors necessary for the differentiation of these cells is lacking in the in vitro assays. The differentiation of cells in diffusion chambers was coincident with a large decrease in levels of LIA obtained from mice with leukemia and is discussed in terms of the concept of remission and relapse of acute leukemia.

Key Words

leukemia diffusion chambers proliferation differentiation 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Broxmeyer, H.E.: Culture characteristics of human granulocyte-macrophage progenitor cells and their regulation in the context of bone marrow transplantation. Exp. Hematol. (Suppl.) 7, 149–158 (1979)Google Scholar
  2. 2.
    Broxmeyer, H.E., Moore, M.A.S.: Communication between white cells and the abnormalities of this in leukemia. Biochim. Biophys. Acta 516, 129–166 (1978)PubMedGoogle Scholar
  3. 3.
    Broxmeyer, H.E., Grossbard, E., Jacobsen, N., Moore, M.A.S.: Evidence for a proliferative advantage of leukemia colony forming cells in vitro. J. Natl. Cancer Inst. 60, 513–521 (1978)PubMedGoogle Scholar
  4. 4.
    Broxmeyer, H.E., Jacobsen, N., Kurland, J., Mendelsohn, N., Moore, M.A.S.: In vitro suppression of normal granulocytic stem cells by inhibitory activity derived from human leukemia cells. J. Natl. Cancer Inst. 60, 497–511 (1978)PubMedGoogle Scholar
  5. 5.
    Broxmeyer, H.E., Smithyman, A., Eger, R.R., Meyers, P.A., De Sousa, M.: Identification of lactoferrin as the granulocyte-derived inhibitor of colony stimulating activity production. J. Exp. Med. 148, 1052–1067 (1978)PubMedCrossRefGoogle Scholar
  6. 6.
    Broxmeyer, H.E., Grossbard, E., Jacobsen, N., Moore, M.A.S.: Persistence of leukemia-associated inhibitory activity against normal granulocyte-macrophage progenitor cells during remission of acute leukemia. N. Engl. J. Med. 301, 346–351 (1979)PubMedCrossRefGoogle Scholar
  7. 7.
    Broxmeyer, H.E., Ralph, P., Margolis, V.B., Nakoinz, I., Meyers, P., Kapoor, N., Moore, M.A.S.: Characteristics of bone marrow and blood cells in human leukemia that produce leukemia inhibitory activity (LIA). Leukemia Res. 3, 193–203 (1979)CrossRefGoogle Scholar
  8. 8.
    Broxmeyer, H.E., Pahwa, R., Jacobsen, N., Pelus, L.M., Ralph, P., Meyers, P.A., Pahwa, S., Kapoor, N.: Specific inhibitory activity against granulocyte progenitor cells produced by non-T lymphocytes from patients with neutropenia. Exp. Hematol. 8, 228–247 (1980)Google Scholar
  9. 9.
    Broxmeyer, H.E., De Sousa, M., Smithyman, A., Raph P., Hamilton, J., Kurland, J.I, Bognacki, U.: Specificity and modulation of the action of lactoferrin, a negative feedback regulator of myleopoeisis. Blood. 55; 324–333 (1980)PubMedGoogle Scholar
  10. 10.
    Chimishkyan, K.L., Belyanchicova, N.I., Kosgrykina, V.N., Meiland, E.N.: The influence of Brucella abortus on the course of acute myeloid leukemia in mice (abstr.) (in Russian). Vopr. Virusol. 2, 202–206 (1977)Google Scholar
  11. 11.
    Fauerholdt, L., Jacobsen, N.: Cultivation of leukemic human bone marrow cells in diffusion chambers implanted into normal and irradiated mice. Blood 45, 495–501 (1975)PubMedGoogle Scholar
  12. 12.
    Hoelzer, D., Kurrle, E., Schmucker, H., Harriss, E.B.: Evidence for differentiation of human leukemic blood cells in diffusion chamber culture. Blood 49, 729–744 (1977)PubMedGoogle Scholar
  13. 13.
    Jacobsen, N., Broxmeyer, H.E., Grossbard, E., Moore, M.A.S.: Diversity of human granulopoietic precursor cells: separation of cells that form colonies in diffusion chambers (CFU-d) from populations of colony forming cells in vitro (CFU-c) by velocity sedimentation. Blood 52, 221–232 (1978)PubMedGoogle Scholar
  14. 14.
    Jacobsen, N., Broxmeyer, H.E., Grossbard, E., Moore, M.A.S.: Colony-forming units in diffusion chambers (CFU-d) and colony forming units in agar culture (CFU-c) obtained from normal human bone marrow: a possible parent-progeny relationship. Cell Tissue Kinet. 12, 213–226 (1979)PubMedGoogle Scholar
  15. 15.
    Koski, I.R., Poplack, D.G., Blaese, R.M.: A non specific esterase stain for the identification of monocytes and macrophages. In: In vitro methods in cell mediated and tumor immunity. Bloom, B.R., David, J.R. (eds.), pp. 359–362. New York: Academic Press 1976Google Scholar
  16. 16.
    Mertelsmann, R., Mertelsmann, I., Koziner, B., Moore, M.A.S., Clarkson, B.D.: Improved biochemical assay for terminal deoxynucleotidyl transferase in human blood cells. Results in 89 adult patients with lymphoid leukemias and malignant lymphomas in leukemic phase. Leukemia Res. 2, 57–70Google Scholar
  17. 17.
    Moore, M.A.S., Broxmeyer, H.E., Sheridan, A.P.C., Meyers, P.A., Jacobsen, N., Winchester, R.J.: Continuous human bone marrow culture: la antigen characterization of probable pluripotential stem cells. Blood 55; 682–690 (1980)PubMedGoogle Scholar
  18. 18.
    Pelus, L.M., Broxmeyer, H.E., Kurland, J.I., Moore, M.A.S.: Regulation of macrophage and granulocyte proliferation: specificities of prostaglandin E and lactoferrin. J. Exp. Med. 150; 227–292 (1979)CrossRefGoogle Scholar
  19. 19.
    Ralph, P., Moore, M.A.S., Nilsson, K.: Lysozyme synthesis by established human murine histiocytic lymphoma cell lines. J. Exp. Med. 143, 1528–1533 (1976)PubMedCrossRefGoogle Scholar
  20. 20.
    Winchester, R.J., Ross, C.D., Jarowski, C.I., Wang, C.Y., Halper, J., Broxmeyer, H.E.: Expression of la-like antigen molecules on human granulocytes during early phases of differentiation. Proc. Natl. Acad. Sci. USA 74, 4012–4016 (1977)PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1980

Authors and Affiliations

  • H. E. Broxmeyer
  • L. Koltun
  • N. Jacobsen
  • M. A. S. Moore

There are no affiliations available

Personalised recommendations