Wotton Sandy, Stewart Monica, Blyth Karen, Vaillant Francois, Kilbey Anna, Neil James C, Cameron Ewan R
Molecular Oncology Laboratory, Institute of Comparative Medicine, University of Glasgow Veterinary School, United Kingdom.
Cancer Res. 2002 Dec 15;62(24):7181-5.
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.
RUNX1/AML1基因是人类白血病中染色体易位的常见靶点。所产生的融合产物的生物学特性，以及单倍体不足会增加患白血病风险这一发现（W-J.宋等人，《自然遗传学》，23: 166 - 175，1999；M.大里田等人，《血液》，93: 1817 - 1824，1999），导致了一种广泛持有的观点，即RUNX1功能丧失是一个关键事件。然而，我们现在报告，在携带MYC癌基因的小鼠的T细胞淋巴瘤中，该基因是插入诱变的靶点，启动子插入导致过表达，而不影响编码序列的完整性。此外，Runx1单倍体不足并不会加速MYC/Runx2转基因或鼠白血病病毒感染小鼠的淋巴瘤发展。这些发现揭示了Runx1基因也可以作为一个显性癌基因，并表明Runx基因家族在人类白血病中的参与可能比以前认识到的更为广泛和复杂。
