Proviral insertion indicates a dominant oncogenic role for Runx1/AML-1 in T-cell lymphoma

Wotton, S., Stewart, M., Blyth, K. , Vaillant, F., Kilbey, A., Neil, J. C. and Cameron, E. R. (2002) Proviral insertion indicates a dominant oncogenic role for Runx1/AML-1 in T-cell lymphoma. Cancer Research, 62(24), pp. 7181-7185. (PMID:12499254)

Abstract

The RUNX1/AML1 gene is a frequent target for chromosomal translocations in human leukemia. The biological properties of the resulting fusion products and the finding that haploinsufficiency increases the risk of developing leukemia (W-J. Song et al., Nat. Genet., 23: 166–175, 1999; M. Osata et al., Blood, 93: 1817–1824, 1999) have led to the widely held view that RUNX1 loss-of-function is a key event. However, we now report that the gene is a target for insertional mutagenesis in T-cell lymphomas of mice carrying a MYC oncogene, where promoter insertion results in overexpression without affecting the integrity of the coding sequence. Moreover, Runx1 haploinsufficiency does not accelerate lymphoma development in MYC/Runx2 transgenic or murine leukemia virus-infected mice. These findings reveal that the Runx1 gene can also act as a dominant oncogene and suggest that the involvement of the Runx gene family in human leukemia may be more widespread and complex than previously realized.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Wotton, Dr Sandra and Blyth, Professor Karen and Cameron, Professor Ewan and Stewart, Dr Monica and Kilbey, Dr Anna and Neil, Professor James
• Authors: Wotton, S., Stewart, M., Blyth, K., Vaillant, F., Kilbey, A., Neil, J. C., and Cameron, E. R.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity; College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine; College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Cancer Research
• Publisher: American Association for Cancer Research
• ISSN: 0008-5472
• ISSN (Online): 1538-7445