The homeobox gene Hex induces T-cell-derived lymphomas when overexpressed in hematopoietic precursor cells
The homeobox gene Hex induces T-cell-derived lymphomas when overexpressed in hematopoietic precursor cells
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DOI：
10.1038/sj.onc.1206822
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发表时间：
2003-10-02
期刊：
影响因子：
8
通讯作者：
Justice, MJ
中科院分区：
文献类型：
--
作者：
George, A;Morse, HC;Justice, MJ
病毒插入位点Lvis1的前病毒插入经常发生在AKXD小鼠的B细胞和T细胞白血病和淋巴瘤中，并激活附近的两个基因，即分歧的同源框基因Hex和动蛋白相关纺锤体蛋白基因EG5。为了确定十六进制错误表达是否会导致造血系分化改变或肿瘤转化，我们将含有十六进制编码区的逆转录病毒转导的骨髓细胞移植到小鼠体内。Hex在造血祖细胞中的高水平表达抑制了这些前体对成熟血细胞谱系的贡献。接受六角形骨髓移植的小鼠也会患上似乎起源于骨髓的血液肿瘤。肿瘤有TCR基因的克隆性重排，是Thy1(+)，是CD4(+)CD8(+)，CD4(-)CD8(-)或混合，表明肿瘤起源于前体T细胞群。移植小鼠的肿瘤包含克隆性和转录活性的Hex前病毒插入，表明Hex错误表达在这些肿瘤的发病中起到了因果作用。我们的结果表明，当Hex在造血祖细胞中错误表达时，可以作为T系癌基因。
Proviral insertions at the viral insertion site Lvis1 occur frequently in B- and T-cell leukemias and lymphomas in AKXD mice and activate two nearby genes, the divergent homeobox gene Hex and the kinesin-related spindle protein gene Eg5. To determine whether Hex misexpression results in the altered differentiation or neoplastic transformation of hematopoietic lineages, we have transplanted mice with bone marrow cells transduced with retrovirus containing the Hex coding region. High levels of Hex expression in hematopoietic precursor cells inhibit contribution to mature blood cell lineages by these precursors. Hex bone marrow transplant recipient mice also develop hematologic neoplasms that appear to originate in the bone marrow. The tumors have clonal rearrangements of the TCR locus, are Thy1(+), and are CD4(+)CD8(+), CD4(-)CD8(-), or mixed, indicating tumor origin from a precursor T-cell population. Tumors in transplant mice contain clonal and transcriptionally active Hex proviral insertions, demonstrating a causal role for Hex misexpression in the onset of these neoplasms. Our results demonstrate that Hex can act as a T lineage oncogene when misexpressed in hematopoietic precursor cells.