Wang J, Wang M, Liu J M
Hematology Branch, National Heart, Lung, and Blood Institute, Bethesda, Maryland 20892, USA.
Cancer Res. 1997 Jul 15;57(14):2951-5.
The (8;21)(q22;q22) translocation, reported in 40% of M2-subtype acute myeloid leukemias (AMLs), is the second-most frequently observed example of a nonrandom genetic alteration associated with AML. Juxtaposition of the AML1 gene on chromosome 21 to the ETO gene on chromosome 8 fuses the NH2-terminal portion of AML1 to near-full length ETO, creating AML1/ETO. Previous work has been focused on perturbation of AML1 gene function by the chimeric fusion protein as a mechanism of leukemogenesis. Here, we demonstrate that ETO itself has transforming properties. Ectopic ETO expression in NIH/3T3 cells led to foci of transformation and colony growth in soft agar. ETO-expressing cells grew to higher saturation densities and induced tumors following injection into irradiated and splenectomized nude mice. Our data suggests that ETO may play an important role in the leukemic transforming potential of the AML1/ETO fusion protein.
在40%的M2型急性髓系白血病（AML）中发现的（8；21）（q22；q22）易位，是与AML相关的非随机基因改变中第二常见的例子。21号染色体上的AML1基因与8号染色体上的ETO基因并列，将AML1的NH2末端部分与接近全长的ETO融合，产生AML1/ETO。先前的研究工作集中在嵌合融合蛋白对AML1基因功能的干扰作为白血病发生的一种机制。在这里，我们证明ETO本身具有转化特性。在NIH/3T3细胞中异位表达ETO导致转化灶形成和软琼脂中的集落生长。表达ETO的细胞生长到更高的饱和密度，并在注射到经照射和脾切除的裸鼠后诱导肿瘤形成。我们的数据表明，ETO可能在AML1/ETO融合蛋白的白血病转化潜能中发挥重要作用。
