Program of Cellular and Molecular Medicine, Children's Hospital, and Immune Disease Institute, Harvard Medical School, Boston, MA 02115, USA.
Cancer Cell. 2012 Aug 14;22(2):167-79. doi: 10.1016/j.ccr.2012.06.012.
In Burkitt lymphoma (BL), a germinal center B-cell-derived tumor, the pro-apoptotic properties of c-MYC must be counterbalanced. Predicting that survival signals would be delivered by phosphoinositide-3-kinase (PI3K), a major survival determinant in mature B cells, we indeed found that combining constitutive c-MYC expression and PI3K activity in germinal center B cells of the mouse led to BL-like tumors, which fully phenocopy human BL with regard to histology, surface and other markers, and gene expression profile. The tumors also accumulate tertiary mutational events, some of which are recurrent in the human disease. These results and our finding of recurrent PI3K pathway activation in human BL indicate that deregulated c-MYC and PI3K activity cooperate in BL pathogenesis.
在伯基特淋巴瘤（BL）中，一种生发中心 B 细胞来源的肿瘤，c-MYC 的促凋亡特性必须得到平衡。预测生存信号将由磷酸肌醇 3-激酶（PI3K）传递，PI3K 是成熟 B 细胞中的主要生存决定因素，我们确实发现，在小鼠的生发中心 B 细胞中同时表达组成性 c-MYC 和 PI3K 活性，会导致类似于 BL 的肿瘤，这些肿瘤在组织学、表面和其他标志物以及基因表达谱方面与人类 BL 完全相似。肿瘤还会积累三级突变事件，其中一些在人类疾病中经常发生。这些结果以及我们在人类 BL 中发现的 PI3K 通路的反复激活表明，失调的 c-MYC 和 PI3K 活性在 BL 的发病机制中合作。
