Pre-B cell proliferation and lymphoblastic leukemia/high-grade lymphoma in Eμ-miR155 transgenic mice
Pre-B cell proliferation and lymphoblastic leukemia/high-grade lymphoma in Eμ-miR155 transgenic mice
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DOI：
10.1073/pnas.0602266103
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发表时间：
2006-05-02
影响因子：
11.1
通讯作者：
Croce, CM
中科院分区：
文献类型：
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作者：
Costinean, S;Zanesi, N;Croce, CM
MicroRNAs(MiRNAs)是一类新发现的转录后调控非编码小RNA，它与靶向mRNAs结合，阻断其翻译或启动其降解。对人和小鼠造血系的miRNA图谱显示，一些miRNAs在造血细胞发育过程中存在差异表达，提示在造血细胞分化中发挥作用。此外，最近的研究表明miRNAs参与了癌症的发生和发展。据报道，miR155及其宿主基因BIC在人类B细胞淋巴瘤中积聚，特别是在弥漫性大B细胞淋巴瘤、霍奇金淋巴瘤和某些类型的Burkitt淋巴瘤中。在这里，我们显示E-MMU-miR155转基因小鼠最初在脾和骨髓表现出明显的白血病前B细胞增殖，随后表现为坦率的B细胞恶性。这些发现表明miR155的作用是诱导多克隆扩增，有利于捕捉次级遗传变化以进行完全转化。
MicroRNAs (miRNAs) represent a newly discovered class of post-transcriptional regulatory noncoding small RNAs that bind to targeted mRNAs and either block their translation or initiate their degradation. miRNA profiling of hematopoietic lineages in humans and mice showed that some miRNAs are differentially expressed during hematopoietic development, suggesting a role in hematopoietic cell differentiation. In addition, recent studies suggest the involvement of miRNAs in the initiation and progression of cancer. miR155 and BIC, its host gene, have been reported to accumulate in human B cell lymphomas, especially in diffuse large B cell lymphomas, Hodgkin lymphomas, and certain types of Burkitt lymphomas. Here, we show that E mu-mmu-miR155 transgenic mice exhibit initially a preleukemic pre-B cell proliferation evident in spleen and bone marrow, followed by frank B cell malignancy. These findings indicate that the role of miR155 is to induce polyclonal expansion, favoring the capture of secondary genetic changes for full transformation.