Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

Acute leukaemia in bcr/abl transgenic mice

Nature volume 344, pages 251–253 (1990)Cite this article

Abstract

THE Philadelphia chromosome, widely implicated in human leukaemia, is the result of a reciprocal translocation t(9;22) (q34;q11) in which the abl oncogene located at 9q34 is translocated to chromosome 22q11, where it is fused head-to-tail with 5" exons of the bcr gene1–8. In acute lymphoblastic leukaemia, some patients have a breakpoint within the major breakpoint cluster region of the bcr gene, whereas others have the break within its first intron6,9–13. This second type of translocation results in the transcription of a 7.0-kilobase chimaeric bcr/abl messenger RNA translated into a bcr/abl fusion protein, p190, which has an abnormal tyrosine kinase activity and is strongly autophosphorylated in vitro14. We have generated mice transgenic for a bcr/abl p190 DNA construct and find that progeny are either moribund with, or die of acute leukaemia (myeloid or lymphoid) 10–58 days after birth. This finding is evidence for a causal relationship between the Philadelphia chromosome and human leukaemia.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Nowell, P. C. & Hungerford, D. A. Science 132, 1497–1499 (1960).

    Google Scholar 

  2. Rowley, J. D. Nature 243, 290–293 (1973).

    Article  ADS  CAS  Google Scholar 

  3. de Klein, A. et al. Nature 300, 765–767 (1982).

    Article  ADS  CAS  Google Scholar 

  4. Sandberg, A., Kohno, S., Wake, N. & Minowada, J. Cancer Genet. Cytogenet. 2, 145–174 (1980).

    Article  Google Scholar 

  5. Priest, J. R. et al. Blood 56, 15–22 (1980).

    CAS  PubMed  Google Scholar 

  6. de Klein, A. et al. Blood 68, 1369–1375 (1986).

    CAS  PubMed  Google Scholar 

  7. Heisterkamp, N., Stam, K., Groffen, J., de Klein, A. & Grosveld, G. Nature 315, 758–761 (1985).

    Article  ADS  CAS  Google Scholar 

  8. Shtivelman, E., Lifshitz, B., Gale, R. B. & Canaani, E. Nature 315, 550–554 (1985).

    Article  ADS  CAS  Google Scholar 

  9. Rodenhuis, S., Smets, L. A., Slater, R. M., Behrendt, H. & Veerman, A. J. P. New Engl. J. Med. 313, 51–52 (1985).

    Article  CAS  Google Scholar 

  10. Erikson, J. et al. Proc. natn. Acad. Sci. U.S.A. 83, 1807–1811 (1986).

    Article  ADS  CAS  Google Scholar 

  11. Heisterkamp, N., Knoppel, E. & Groffen, J. Nucleic Acids Res. 16, 10069–10081 (1988).

    Article  CAS  Google Scholar 

  12. Hermans, A. et al. Cell 51, 33–40 (1987).

    Article  CAS  Google Scholar 

  13. Heisterkamp, N. et al. Blood 73, 1307–1311 (1989).

    CAS  PubMed  Google Scholar 

  14. Kurzrock, R., Gutterman, J. U. & Talpas, M. New Engl. J. Med. 319, 990–998 (1988).

    Article  CAS  Google Scholar 

  15. Palmiter, R., Norstedt, G., Gelinas, R. E., Hammer, R. E. & Brinster, R. L. Science 222, 809–814 (1983).

    Article  ADS  CAS  Google Scholar 

  16. Stuart, G. W., Searle, P. F., Chen, H. Y., Brinster, R. L. & Palmiter, R. D. Proc. natn. Acad. Sci. U.S.A. 81, 7318–7322 (1984).

    Article  ADS  CAS  Google Scholar 

  17. Kawasaki, E. S. et al. Proc. natn. Acad. Sci. U.S.A. 85, 5698–5702 (1988).

    Article  ADS  CAS  Google Scholar 

  18. Coffman, R. L. Immunol. Rev. 69, 5–23 (1983).

    Article  CAS  Google Scholar 

  19. Hariharan, I. K. et al. Molec. cell. Biol. 9, 2798–2805 (1989).

    Article  CAS  Google Scholar 

  20. Holmes, K. L., Pierce, W. F., Davidson, W. F. & Morse III, H. C. J. exp. Med. 164, 443–457 (1986).

    Article  CAS  Google Scholar 

  21. Davidson, W. F., Pierce, J. H., Rudikoff, S. & Morse III, H. C. J. exp. Med. 168, 389–407 (1988).

    Article  CAS  Google Scholar 

  22. Hanecak, R., Zovich, D. C., Pattengale, P. K. & Fan, H. Molec. cell. Biol. 9, 2264–2268 (1989).

    Article  CAS  Google Scholar 

  23. Ribeiro, R. C. et al. Blood 70, 948–951 (1987).

    CAS  PubMed  Google Scholar 

  24. Rivera G. K., Santana, V. M., Pui, C-H., Furman, W. L. & Kalwinsky, D. K. in Acute Lymphoblastic Leukemia (eds Gale, R. P. & Hoelzer, D.) 143–146 (Wiley-Liss, New York. 1989).

    Google Scholar 

  25. Bloomfield C. D. et al. in Acute Lymphoblastic Leukemia (eds Gale, R. P. & Hoelzer, D.) 101–110 (Wiley-Liss, New York, 1989).

    Google Scholar 

  26. McLaughlin, J., Chianese, E. & Witte, O. N. Molec. cell. Biol. 9, 1866–1874 (1989).

    Article  CAS  Google Scholar 

  27. Greaves, M. F. in Acute Lymphoblastic Leukemia (eds Gale, R. P. & Hoelzer, D.) 1–14 (Wiley-Liss, New York, 1989).

    Google Scholar 

  28. Grosveld, G. in Acute Lymphoblastic Leukemia (eds Gale, R. P. & Hoelzer. D.) 15–28 (Wiley-Liss, New York, 1989).

    Google Scholar 

  29. Heisterkamp, N., Groffen, J. & Stephenson, J. R. J. appl. Genet. 2, 57–68 (1983).

    CAS  Google Scholar 

  30. Hogan, B., Constantini, F. & Lacy, E. Manipulating the Mouse Embryo (Cold Spring Harbor Laboratory, New York, 1986).

    Google Scholar 

  31. Chomcznski, P. & Sacchi, N. Analyt Biochem. 162, 156–159 (1987).

    Google Scholar 

Download references

Author information

Author notes

  1. John Groffen: To whom correspondence should be addressed.

Authors and Affiliations

  1. Section of Molecular Diagnosis, Department of Pathology, Children's Hospital of Los Angeles, 4650 Sunset Boulevard, Los Angeles, California, 90027, USA

    Nora Heisterkamp, Guido Jenster, Joanne ten Hoeve & John Groffen

  2. Section of Hematopathology, Department of Pathology, Children's Hospital of Los Angeles, 4650 Sunset Boulevard, Los Angeles, California, 90027, USA

    Daniel Zovich & Paul K. Pattengale

Authors
  1. Nora Heisterkamp
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Guido Jenster
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Joanne ten Hoeve
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Daniel Zovich
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Paul K. Pattengale
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. John Groffen
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Heisterkamp, N., Jenster, G., ten Hoeve, J. et al. Acute leukaemia in bcr/abl transgenic mice. Nature 344, 251–253 (1990). https://doi.org/10.1038/344251a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/344251a0

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing