ts-Oncogene-Transformed Erythroleukemic Cells: A Novel Test System for Purifying and Characterizing Avian Erythroid Growth Factors

  • E. Kowenz
  • A. Leutz
  • G. Döderlein
  • T. Graf
  • H. Beug
Part of the Haematology and Blood Transfusion / Hämatologie und Bluttransfusion book series (HAEMATOLOGY, volume 31)


An emerging, important characteristic of many leukemic cell types is their altered dependence on and/or response to hematopoietic growth factors [6, 17]. In mammals, many of these growth-regulatory proteins have been purified and the respective genes molecularly cloned [16, 26], but the mechanism by which they regulate growth and differentiation of normal hematopoietic precursors is still poorly understood. This is due partly to the fact that such hematopoietic precursors do not self-renew in vitro and constitute only a minor fraction of bone marrow cells, precluding their purification in large numbers [25]. One particularly successful approach to circumventing this problem was the use of avian retroviral oncogenes that transform hematopoietic precursors [10].


Erythroid Cell Erythroid Differentiation Hematopoietic Precursor Chicken Serum Tyrosine Kinase Oncogene 
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  1. 1.
    Beug H, Palmieri S, Freudenstein C, Zentgraf H, Graf T (1982) Hormone-dependent terminal differentiation in vitro of chicken erythroleukemia cells transformed by ts mutants of avian erythroblastosis virus. Cell 28:907–919PubMedCrossRefGoogle Scholar
  2. 2.
    Beug H, Hayman MJ, Graf T, Benedict SH, Wallbank AM, Vogt PK (1985) S13, a rapidly oncogenic replication-defective avian retro-virus. Virology 145:141–153PubMedCrossRefGoogle Scholar
  3. 3.
    Beug H, Kahn P, Doederlein G, Hayman MJ, Graf T (1985) Characterization of hematopoietic cells transformed in vitro by AEV-H, an erbB-containing avian erythroblastosis virus. In: Neth R, Gallo R, Greaves M, Janka K (eds) Modern trends in human leukemia, VI. Springer, Berlin Heidelberg New York Tokyo, pp 290–297Google Scholar
  4. 4.
    Beug H, Kahn P, Vennstroem B, Hayman MJ, Graf T (1985) How do retroviral oncogenes induce transformation in avian erythroid cells? Proc R Soc London [Biol] 226:121–126CrossRefGoogle Scholar
  5. 5.
    Coll J, Ingram VM (1981) Identification of ovotransferrin as a heme-, colony- and burst-stimulating factor in chick erythroid cell cultures. Exp Cell Res 131:173–184PubMedCrossRefGoogle Scholar
  6. 6.
    Cook WD, Metcalf D, Nicola N, Burgess A, Walker F (1985) Malignant transformation of a growth factor-dependent myeloid cell line by Abelson virus without evidence of an autocrine mechanism. Cell 41:677–683PubMedCrossRefGoogle Scholar
  7. 7.
    Frykberg L, Palmieri S, Beug H, Graf T, Hayman MJ, Vennstroem B (1983) Transforming capacities of avian erythroblastosis virus mutants deleted in the erbA or erbB oncogenes. Cell 32:227–238PubMedCrossRefGoogle Scholar
  8. 8.
    Gazzolo L, Moscovici C, Moscovici MG, Samarut J (1979) Response of hemopoietic cells to avian acute leukemia viruses: effects on the differentiation of the target cells. Cell 16:627–638PubMedCrossRefGoogle Scholar
  9. 9.
    Graf T, Ade N, Beug H (1978) Temperature-sensitive mutant of avian erythroblastosis virus suggests a block of differentiation as mechanism of leukaemogenesis. Nature 257:496–501CrossRefGoogle Scholar
  10. 10.
    Graf T, Beug H (1978) Avian leukemia viruses: interaction with their target cells in vivo and in vitro. BBA Revs Cancer 516:269–299Google Scholar
  11. 11.
    Graf T, von Kirchbach A, Beug H (1981) Characterization of the hematopoietic target cells of AEV, MC29 and AMV avian leukemia viruses. Exp Cell Res 131:331–343PubMedCrossRefGoogle Scholar
  12. 12.
    Kahn P, Adkins B, Beug H, Graf T (1984) Src- and fps-containing avian sarcoma viruses transform chicken erythroid cells. Proc Natl Acad Sci USA 81:7122–7126PubMedCrossRefGoogle Scholar
  13. 13.
    Kahn P, Frykberg L, Brady C, Stanley IJ, Beug H, Vennstroem B, Graf T (1986) V-erbA cooperates with sarcoma oncogenes in leukemic cell transformation. Cell 45:349–356PubMedCrossRefGoogle Scholar
  14. 14.
    King GL, Kahn CR (1981) Non-parallel evolution of metabolic and growth-promoting function of insulin. Nature 292:644–646PubMedCrossRefGoogle Scholar
  15. 15.
    Leutz A, Beug H, Graf T (1984) Purification and characterization of cMGF, a novel chicken myelomonocytic growth factor. EMBO J 3:3191–3197PubMedGoogle Scholar
  16. 16.
    Nicola NA, Metcalf D (1984) Binding of the differentiation-inducer, granulocyte-colony-stimulating factor to responsive but not unresponsive leukemia cell lines. Proc Natl Acad Sci USA 81:3765–3769PubMedCrossRefGoogle Scholar
  17. 17.
    Pierce JH, DiGiore PP, Aaronson SA, Potter M, Pumphrey J, Scott A, Ihle JN (1985) Neoplastic transformation of mast cells by Abelson-MuLV: abrogation of IL-3 dependence by a nonautocrine mechanism. Cell 41:685–693PubMedCrossRefGoogle Scholar
  18. 18.
    Petrides PE, Bohler P (1980) The mitogenic activity of insulin: an intrinsic property of the molecule. Biochem Biophys Res Commun 95:1138–1141PubMedCrossRefGoogle Scholar
  19. 19.
    Radke K, Beug H, Kornfeld S, Graf T (1982) Transformation of both erythroid and myeloid cells by E26, an avian leukemia virus that contains the myb gene. Cell 31:643–653PubMedCrossRefGoogle Scholar
  20. 20.
    Samarut J (1978) Isolation of an erythropoietic stimulating factor from the serum of anemic chicks. Exp Cell Res 115:123–126PubMedCrossRefGoogle Scholar
  21. 21.
    Samarut J, Gazzolo L (1982) Target cells infected by avian erythroblastosis virus differentiate and become transformed. Cell 28:921–929PubMedCrossRefGoogle Scholar
  22. 22.
    Spivak JL, Small D, Shaper JH, Hollenberg MD (1978) Use of immobilized lectin and other ligands for the partial purification of erythropoietin. Blood 52:1178–1186PubMedGoogle Scholar
  23. 23.
    Spivak JL, Small D, Hollenberg MD (1977) Erythropoietin: isolation by affinity chromatography with lectin-agarose derivates. Proc Natl Acad Sci USA 74:4633–4635PubMedCrossRefGoogle Scholar
  24. 24.
    Schmidt JA, Marshall J, Hayman MJ, Ponka P, Beug H (1986) Control of erythroid differentiation: possible role of the transferrin cycle. Cell 46:41–51PubMedCrossRefGoogle Scholar
  25. 25.
    van Zant G, Goldwasser E (1984) Erythropoietin and its target cells. In: Guroff G (ed) Growth and maturation factors, vol 2. Wiley, New YorkGoogle Scholar
  26. 26.
    Walker F, Burgess AW (1985) Specific binding of radioiodinated granulocyte-macrophage colony stimulating factor to hematopoietic cells. EMBO J 4:933–939PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1987

Authors and Affiliations

  • E. Kowenz
    • 1
  • A. Leutz
    • 1
  • G. Döderlein
    • 1
  • T. Graf
    • 1
  • H. Beug
    • 1
  1. 1.European Molecular Biology LaboratoryHeidelbergGermany

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