Carella C, Bonten J, Sirma S, Kranenburg T A, Terranova S, Klein-Geltink R, Shurtleff S, Downing J R, Zwarthoff E C, Liu P P, Grosveld G C
Department of Genetics and Tumor Cell Biology, St Jude Children's Research Hospital, Memphis, TN 38105-0318, USA.
Leukemia. 2007 Aug;21(8):1679-90. doi: 10.1038/sj.leu.2404778. Epub 2007 May 24.
The gene encoding the transcriptional co-activator MN1 is the target of the reciprocal chromosome translocation (12;22)(p13;q12) in some patients with acute myeloid leukemia (AML). In addition, expression array analysis showed that MN1 was overexpressed in AML specified by inv(16), in some AML overexpressing ecotropic viral integration 1 site (EVI1) and in some AML without karyotypic abnormalities. Here we describe that mice receiving transplants of bone marrow (BM) overexpressing MN1 rapidly developed myeloproliferative disease (MPD). This BM also generated myeloid cell lines in culture. By mimicking the situation in human inv(16) AML, forced coexpression of MN1 and Cbfbeta-SMMHC rapidly caused AML in mice. These findings identify MN1 as a highly effective hematopoietic oncogene and suggest that MN1 overexpression is an important cooperative event in human inv(16) AML.
在一些急性髓系白血病（AML）患者中，编码转录共激活因子MN1的基因是相互染色体易位（12；22）（p13；q12）的靶点。此外，表达阵列分析显示，MN1在由inv（16）指定的AML、一些过表达嗜异性病毒整合1位点（EVI1）的AML以及一些无核型异常的AML中过表达。在此我们描述，接受过表达MN1的骨髓（BM）移植的小鼠迅速发展为骨髓增殖性疾病（MPD）。这种BM在培养中也产生了髓系细胞系。通过模拟人类inv（16）AML中的情况，MN1和Cbfbeta-SMMHC的强制共表达迅速在小鼠中引发了AML。这些发现确定MN1为一种高效的造血癌基因，并表明MN1过表达是人类inv（16）AML中的一个重要协同事件。
