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:

Structural organization of the bcr gene and its role in the Ph′ translocation

Abstract

The Philadelphia (Ph′) chromosome, an abnormal chromosome 22 (ref. 1), is one of the best-known examples of a specific human chromosomal abnormality strongly associated with one form of human leukaemia, chronic myelocytic leukaemia (CML). The finding2 that a small region of chromosome 9 which includes the c-abl oncogene is translocated to chromosome 22 prompted studies to elucidate the molecular mechanisms involved in this disease. We have demonstrated previously that the chromosome 9 of one patient with CML contains a breakpoint 14 kilobases (kb) 5′ of the most 5′ v-abl-homologous exon3. These data suggest a role for c-abl in CML, a theory supported by the presence of an abnormally sized abl messenger RNA4,5 and protein6 in the CML cell line K562. The region involved in the translocation on chromosome 22 has also been identified: all Ph′-positive patients examined to date have a breakpoint within a 5.8-kb region, for which we have proposed the name ‘breakpoint cluster region’ (bcr)7. To determine whether her contains protein-encoding regions, probes from bcr were tested for their ability to hybridize to complementary DNA sequences. A 0.6-kb HindIII/BamHl bcr restriction enzyme fragment proved suitable for isolating several cDNA clones from a human fibroblast cDNA library8. Using bcr cDNA sequences, we obtained data strongly suggesting the presence of a chimaeric bcr/abl mRNA in the leukaemic cells of Ph′-positive CML patients. The recent isolation of cDNA clones containing bcr and abl sequences confirms this finding12. Because the bcr part of the chimaeric mRNA could be required to induce the transforming activity of the human c-abl oncogene, we have now initiated studies to characterize the normal ‘bcr gene’ and to determine the effect of a translocation within its coding domain. We demonstrate that as a result of the Ph′ translocation, a variable number of bcr exons are included in the chimaeric bcr/abl mRNA. The bcr gene sequences in this mRNA could be responsible for the transition of the abl cellular proto-oncogene into an oncogene.

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

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

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

Similar content being viewed by others

References

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

    Article  CAS  ADS  Google Scholar 

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

    Article  CAS  ADS  Google Scholar 

  3. Heisterkamp, N. et al. Nature 306, 239–242 (1983).

    Article  CAS  ADS  Google Scholar 

  4. Collins, S. J., Kubonishi, I., Miyoshi, I. & Groudine, M. T. Science 225, 72–74 (1984).

    Article  CAS  ADS  Google Scholar 

  5. Gale, R. P. & Canaani, E. Proc. natn. Acad. Sci. U.S.A. 81, 5648–5652 (1984).

    Article  CAS  ADS  Google Scholar 

  6. Konopka, J. B., Watanabe, S. M. & Witte, O. N. Cell 317, 1035–1042 (1984).

    Article  Google Scholar 

  7. Groffen, J. et al. Cell 36, 93–99 (1984).

    Article  CAS  Google Scholar 

  8. Okayama, H. & Berg, P. Molec. Cell Biol. 3, 280–289 (1983).

    Article  CAS  Google Scholar 

  9. Bartram, C. R. et al. Nature 306, 277–280 (1983).

    Article  CAS  ADS  Google Scholar 

  10. Lipman, D. F. & Pearson, W. R. Science 227, 1435–1441 (1985).

    Article  CAS  ADS  Google Scholar 

  11. Bartram, C. R. et al. EMBO J. 4, 683–686 (1985).

    Article  CAS  Google Scholar 

  12. Canaani, E. et al. Nature 315, 550–554 (1985).

    Article  ADS  Google Scholar 

  13. Groffen, J., Heisterkamp, N., Reynolds, F. Jr & Stephenson, J. R. Nature 304, 167–169 (1983).

    Article  CAS  ADS  Google Scholar 

  14. Sanger, F., Nicklen, S. & Coulson, A. R. Proc. natn. Acad. Sci. U.S.A. 74, 5463–5467 (1977).

    Article  CAS  ADS  Google Scholar 

  15. Messing, J. & Vieira, J. Gene 19, 269–276 (1982).

    Article  CAS  Google Scholar 

  16. Groffen, J., Heisterkamp, N., Blennerhassett, G. & Stephenson, J. R. Virology 126, 213–227 (1983).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Heisterkamp, N., Stam, K., Groffen, J. et al. Structural organization of the bcr gene and its role in the Ph′ translocation. Nature 315, 758–761 (1985). https://doi.org/10.1038/315758a0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/315758a0

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

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