Dysregulated Activation of a Haemopoietic Growth Factor Gene Alone is Insufficient to Cause Malignant Haemopoietic Disease in Normal Haemopoietic Cells
Conceptually, autostimulation of haemopoietic cells is an attractive hypothesis for leukaemic transformation. Many reports based on experiments with haemopoietic growth factor dependent cell lines have documented that autonomous production of the growth factor causes the previously non-tumorigenic cell line to produce fatal tumours (Schräder and Crapper, 1983; Lang et al., 1985; Hapel et al., 1986; Laker et al., 1987; Wong et al., 1987). Whether such experiments have relevance to human leukaemia development, however, remains questionable. In the first instance, the murine cell lines used have acquired a number of genetic changes as is readily evident from their abnormal karyotype. Secondly, the development of these immortalised but haemopoietic growth factor dependent cell lines is readily achieved with murine cells but is an extremely rare event using human cells.
KeywordsAgar Leukemia Myeloma Mast
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- Chang JM, Metealf D, Lang RA, Gonda TJ, Johnson GR (1989) Non-neoplastic hemopoietic myeloproliferative syndrome induced by dysregulated multi-CSF (IL- 3) expression. Blood (in press)Google Scholar
- Hariharan IK, Adams JM, Cory S (1988) bcr-abl oncogene renders myeloid cell line factor independent: potential autocrine mechanism in chronic myeloid leukemia. Oncogene Res (in press)Google Scholar
- Johnson GR, Gonda TJ, Metealf D, Hariharan IK, Cory S (1989) A lethal myelo proliferative syndrome in mice transplanted with bone marrow cells infected with a retrovirus expressing granulocyte-macrophage colony stimulating factor. EMBO J (in press)Google Scholar
- Laker C, Stocking C, Bergholz U, Hess N, DeLamarter JF, Ostertag W (1987) Autocrine stimulation after transfer of the granulocyte/macrophage colony stimulating factor gene and autonomous growth are distinct but interdependent steps in the oncogenic pathway. Proc Natl Acad Sci USA 84: 8458 8462Google Scholar
- Metealf D (1984) The hemopoietic colony stimulating factors. Elsevier, Amsterdam Metealf D (1985) In: Stamatoyannopoulos G, Nienhuis AW (eds) Experimental approaches for the study of hemoglobin switching. Prog Clin Biol Res 191:323–337Google Scholar
- Moore MAS (1988) Interleukin 3: the Panspecific hemopoietin. In: Schrader JW (ed) Lymphokines, vol 15. Academic Press, San Diego, p 254Google Scholar
- Pierce JH, DiFiore 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: 658–693Google Scholar