MLL is essential for NUP98-HOXA9-induced leukemia
MLL is essential for NUP98-HOXA9-induced leukemia
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DOI：
10.1038/leu.2017.62
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发表时间：
2017-10-01
期刊：
影响因子：
11.4
通讯作者：
Kitabayashi, I.
中科院分区：
文献类型：
--
作者：
Shima, Y.;Yumoto, M.;Kitabayashi, I.
涉及NUP 98基因的重排导致与几个伴侣基因的融合发生在急性髓性白血病和骨髓增生异常综合征中。这项研究表明，NUP 98-HOXA 9融合蛋白的NUP 98部分的第二个FG重复结构域对于其细胞永生化和白血病发生活性是重要的。我们证明NUP 98-HOXA 9通过这个FG重复结构域与混合谱系白血病（MLL）相互作用，并且在没有MLL的情况下，NUP 98-HOXA 9诱导的细胞永生化和白血病发生被严重抑制。分子分析表明，MLL对于NUP 98-HOXA 9募集到HOXA基因座和NUP 98-HOXA 9诱导的HOXA基因表达是重要的。我们的数据表明MLL对于NUP 98-HOXA 9白血病的起始是至关重要的。
Rearrangements involving the NUP98 gene resulting in fusions to several partner genes occur in acute myeloid leukemia and myelodysplastic syndromes. This study demonstrates that the second FG repeat domain of the NUP98 moiety of the NUP98-HOXA9 fusion protein is important for its cell immortalization and leukemogenesis activities. We demonstrate that NUP98-HOXA9 interacts with mixed lineage leukemia (MLL) via this FG repeat domain and that, in the absence of MLL, NUP98-HOXA9-induced cell immortalization and leukemogenesis are severely inhibited. Molecular analyses indicate that MLL is important for the recruitment of NUP98-HOXA9 to the HOXA locus and for NUP98-HOXA9-induced HOXA gene expression. Our data indicate that MLL is crucial for NUP98-HOXA9 leukemia initiation.