Tumorigenesis in mice with a fusion of the leukaemia oncogene MII and the bacterial lacZ gene
Tumorigenesis in mice with a fusion of the leukaemia oncogene MII and the bacterial lacZ gene
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DOI：
10.1093/emboj/19.5.843
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发表时间：
2000-03-01
期刊：
影响因子：
11.4
通讯作者：
Rabbitts, TH
中科院分区：
文献类型：
--
作者：
Dobson, CL;Warren, AJ;Rabbitts, TH
在急性白血病中，染色体11 q23处发生许多不同的染色体易位。分子分析显示，ALL基因（也称为ALL-1，HRX或HTRX）被易位破坏，导致与其他染色体的基因融合。MLL融合伴侣的多样性对融合蛋白在肿瘤发展中的功能提出了难题。通过在小鼠胚胎干细胞中使用同源重组将MII的外显子8与细菌lacZ基因连接，分析了R-ILL截短和融合的结果。我们表明，这种融合足以导致胚胎干细胞衍生的急性白血病在嵌合小鼠，这些肿瘤发生与MLL-Af 9嵌合小鼠中发现的那些相比，具有较长的潜伏期。这些研究结果表明，MLL融合蛋白可以有助于肿瘤发生，即使融合伴侣没有已知的致病作用。因此，MLL的截短和融合对于肿瘤发生可能是足够的，而不管融合伴侣如何。
Many different chromosomal translocations occur in man at chromosome 11q23 in acute leukaemias. Molecular analyses revealed that the ALL gene (also called ALL-1, HRX or HTRX) is broken by the translocations, causing fusion with genes from other chromosomes. The diversity of MLL fusion partners poses a dilemma about the function of the fusion proteins in tumour de development. The consequence of R-ILL truncation and fusion has been analysed by joining exon 8 of Mll with the bacterial lacZ gene using homologous recombination in mouse embryonic stem cells. We show that this fusion is sufficient to cause embryonic stem cell-derived acute leukaemias in chimeric mice, and these tumours occur with long latency compared with those found in MLL-Af9 chimeric mice, These findings indicate that an MLL fusion protein can contribute to tumorigenesis, even if the fusion partner has no known pathogenic role. Thus, truncation and fusion of MLL can be sufficient for tumorigenesis, regardless of the fusion partner.