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Constitutive synthesis of interleukin-3 by leukaemia cell line WEHI-3B is due to retroviral insertion near the gene

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Abstract

Interleukin-3 (multi-CSF) is a multilineage haematopoietic growth regulator that initiates the proliferation and differentiation of multipotential stem cells1–5. Complementary DNA clones encoding interleukin-3 (IL-3) have recently been isolated6,7 and the structure of the IL-3 gene determined8,9. IL-3 is produced by T lymphocytes or T lymphomas only after stimulation with antigens, mitogens or chemical activators such as phorbol esters. The myelomonocytic leukaemia line WEHI-3B10,11 also produces IL-3 but its production is constitutive12–14 and the WEHI-3B cells do not appear to produce significant levels of any of the other lymphokines normally secreted by T lymphocytes after stimulation. It has been proposed that the genetic change leading to the constitutive expression of IL-3 may have been a key event in the development of this leukaemia2,3,15,16. We report here that the constitutive synthesis of IL-3 by the WEHI-3B cell line is due to the insertion of an endogenous retrovirus-like element close to the 5′ end of the gene. The insertion, an intracisternal A particle (IAP) genome, is positioned with its 5′ long terminal repeat (LTR) close to the promoter region of the IL-3 gene, resulting in constitutive synthesis of IL-3.

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Authors and Affiliations

  1. Medical Molecular Biology Unit, John Curtin School of Medical Research, Australian National University, PO Box 334, Canberra, ACT, 2601, Australia

    S. Ymer, W. Q. J. Tucker, H. D. Campbell & I. G. Young

  2. Department of Medicine and Clinical Science, John Curtin School of Medical Research, Australian National University, PO Box 334, Canberra, ACT, 2601, Australia

    A. J. Hapel

  3. National Institute for Medical Research, The Ridgeway, Mill Hill, London, NW7 1AA, UK

    C. J. Sanderson

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  1. S. Ymer
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  2. W. Q. J. Tucker
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  3. C. J. Sanderson
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  4. A. J. Hapel
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  5. H. D. Campbell
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  6. I. G. Young
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Ymer, S., Tucker, W., Sanderson, C. et al. Constitutive synthesis of interleukin-3 by leukaemia cell line WEHI-3B is due to retroviral insertion near the gene. Nature 317, 255–258 (1985). https://doi.org/10.1038/317255a0

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