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.

  • News & Views
  • Published:

A new angle on a pervasive oncogene

Nature Genetics volume 23, pages 134–135 (1999)Cite this article

Human cancers result from a multistep pathogenesis associated with the progressive accumulation of mutations in proto-oncogenes and tumour-suppressor genes. This mechanism accounts for the frequent occurrence of dysplastic lesions before the development of life-threatening cancers. Furthermore, the neoplastic process can be jump-started by inheritance of mutant alleles in tumour-suppressor genes, as is the case in rare families whose members are predisposed to the development of cancer. These families are particularly useful for identifying genes whose function is important for the suppression of malignant transformation, mostly for cancers of epithelial cells (carcinomas). In contrast, an inherited susceptibility to leukaemia is exceedingly rare and most pedigrees are too small for linkage studies. Geneticists have therefore concentrated on analysing somatically acquired mutations, in particular, the chromosomal translocations, in an attempt to isolate genes whose mutation contributes to leukaemia pathogenesis. On page 166, Woojoo Song and colleagues1 identify the gene whose mutation underlies the rare autosomal dominant disease known as familial platelet disorder with predisposition to acute myelogenous leukaemia (FPD/AML). They identify CBFA2, which has emerged in recent years as the most frequent target for chromosomal translocations associated with leukaemias2. This study sheds new light on the pervasive role of CBFA2 in human leukaemia pathogenesis and has implications for understanding how leukaemias arise.

The CBFs make important contributions to developmental processes and are targeted by mutations in human diseases. CBFα1 is essential for osteoblast differentiation and bone development4,5; mice deficient in Cbfa1 display a complete lack of bone formation. In humans, haploinsufficiency of CBFA1 results in cleidocranial dysplasia, an autosomal dominant disorder of skeletal morphogenesis6. CBFα2, on the other hand, contributes to haematopoiesis. Mice deficient in either Cbfa2 or Cbfb display a lack of definitive haematopoiesis in the fetal liver7,8,9. Ongoing studies suggest that both proteins are required for the emergence of definitive haematopoietic cells from haemogenic endothelia in the developing embryo3.

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

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

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

Figure 1: Multiple routes to a common pathway in leukaemias.

References

  1. Song, W.-J. et al. Nature Genet. 23, 166– 175 (1999).

    Article  CAS  Google Scholar 

  2. Look, A.T. Science 278, 1059–1064 ( 1997).

    Article  CAS  Google Scholar 

  3. Speck, N.A. et al. Cancer Res. 59, 1789– 1793 (1999).

    Google Scholar 

  4. Otto, F. et al. Cell 89, 765–772 (1997).

    Article  CAS  Google Scholar 

  5. Komori, T. et al. Cell 89, 755–764 (1997).

    Article  CAS  Google Scholar 

  6. Mundlos, S. et al. Cell 89, 773–780 (1997).

    Article  CAS  Google Scholar 

  7. Okuda, T. et al. Cell 84, 321–330 (1996).

    Article  CAS  Google Scholar 

  8. Wang, Q. et al. Proc. Natl Acad. Sci. USA 93, 3444– 3449 (1996).

    Article  CAS  Google Scholar 

  9. Wang, Q. et al. Cell 87, 697–708 (1996).

    Article  CAS  Google Scholar 

  10. Lutterbach, B. et al. Mol. Cell. Biol. 18, 7176– 7184 (1998).

    Article  CAS  Google Scholar 

  11. Wang, J., Hoshino, T., Redner, R.L., Kajigaya, S. & Liu, J.M. Proc. Natl Acad. Sci. USA 95, 10860–10865 (1998).

    Article  CAS  Google Scholar 

  12. Liu, P. et al. Science 261, 1041–1044 (1993).

    Article  CAS  Google Scholar 

  13. Osato, M. et al. Blood 93, 1817–1824 (1999).

    CAS  Google Scholar 

  14. Catilla, L.H. et al. Nature Genet. 23, 144– 146 (1999).

    Article  Google Scholar 

  15. Fero, M.L., Randel, E., Gurley, K.E., Robert, J.M. & Kemp, C. et al. Nature 396, 177 –180 (1998).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pathology, Stanford University School of Medicine, Stanford, 94305-5324 , California, USA

    Michael L Cleary

Authors
  1. Michael L Cleary
    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

Cleary, M. A new angle on a pervasive oncogene. Nat Genet 23, 134–135 (1999). https://doi.org/10.1038/13761

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/13761

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