EB-1, a tyrosine kinase signal transduction gene, is transcriptionally activated in the t(1;19) subset of pre-B ALL, which express oncoprotein E2a-Pbx1
EB-1, a tyrosine kinase signal transduction gene, is transcriptionally activated in the t(1;19) subset of pre-B ALL, which express oncoprotein E2a-Pbx1
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DOI：
10.1038/sj.onc.1202874
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发表时间：
1999-09-02
期刊：
影响因子：
8
通讯作者：
Kamps, MP
中科院分区：
文献类型：
--
作者：
Fu, XY;McGrath, S;Kamps, MP
t（1; 19）前B细胞急性淋巴细胞白血病（ALL）的易位产生E2 a-Pbx 1，一种含有E2 a的反式激活结构域连接到同源结构域蛋白Pbx 1的嵌合癌蛋白，E2 a-Pbx 1在小鼠中引起T细胞和髓样白血病，阻断培养的髓样祖细胞的分化，并通过伴随组织特异性和发育调节基因的异常表达的机制转化成纤维细胞。在这里，我们调查是否异常基因表达也发生在特定的t（1;19）的前B细胞ALL在man. Two新的基因，EB-1和EB-2，以及钙调蛋白在每个转录激活的7个t（1;19）细胞系的子集。EB-1表达在与t（1;19）无关的前B ALL患者的骨髓中极低，而在与t（1; 19）相关的前B ALL患者的骨髓中升高超过100倍。正常EB-1表达，在脑和睾丸中较强，相同的组织表现出最高水平的PBX 1表达。EB-1编码一种信号蛋白，其含有与dNumb发育调节因子同源的磷酸酪氨酸结合结构域和与Eph受体酪氨酸激酶C-末端尾部同源的两个SAM结构域。我们的结论是组织特异性基因的异常表达是t（1;19）pre-B ALL的一个特征，正如以前在E2 a-Pbx 1转化的成纤维细胞中发现的那样。EB-1过表达可能干扰控制增殖或分化的正常信号传导。
The t(1;19) translocation of pre-B cell acute lymphocytic leukemia (ALL) produces E2a-Pbx1, a chimeric oncoprotein containing the transactivation domains of E2a joined to the homeodomain protein, Pbx1, E2a-Pbx1 causes T cell and myeloid leukemia in mice, blocks differentiation of cultured myeloid progenitors, and transforms fibroblasts through a mechanism accompanied by aberrant expression of tissue-specific and developmentally-regulated genes. Here we investigate whether aberrant gene expression also occurs specifically in the t(1;19)-containing subset of pre-B cell ALL in man. Two new genes, EB-1 and EB-2, as well as Caldesmon were transcriptionally activated in each of seven t(1;19) cell Lines. EB-1 expression was extremely low in marrow from patients having pre-B ALL not associated with the t(1;19), and elevated more than 100-fold in marrow from patients with pre-B ALL associated with the t(1;19), Normal EB-1 expression,vas strong in brain and testis, the same tissues exhibiting the highest levels of PBX1 expression. EB-1 encodes a signaling protein containing a phosphotyrosine binding domain homologous to that of dNumb developmental regulators and two SAM domains homologous to those in the C-terminal tail of Eph receptor tyrosine kinases. We conclude that aberrant expression of tissue-specific genes is a characteristic of t(1;19) pre-B ALL, as was previously found in fibroblasts transformed by E2a-Pbx1, Potentially, EB-1 overexpression could interfere with normal signaling controlling proliferation or differentiation.