Burkitt lymphoma pathogenesis and therapeutic targets from structural and functional genomics.
Burkitt lymphoma pathogenesis and therapeutic targets from structural and functional genomics.
复制标题
DOI：
10.1038/nature11378
复制
发表时间：
2012-10-04
期刊：
影响因子：
64.8
通讯作者：
Staudt, Louis M.
中科院分区：
文献类型：
--
作者：
Schmitz, Roland;Young, Ryan M.;Ceribelli, Michele;Jhavar, Sameer;Xiao, Wenming;Zhang, Meili;Wright, George;Shaffer, Arthur L.;Hodson, Daniel J.;Buras, Eric;Liu, Xuelu;Powell, John;Yang, Yandan;Xu, Weihong;Zhao, Hong;Kohlhammer, Holger;Rosenwald, Andreas;Kluin, Philip;Mueller-Hermelink, Hans Konrad;Ott, German;Gascoyne, Randy D.;Connors, Joseph M.;Rimsza, Lisa M.;Campo, Elias;Jaffe, Elaine S.;Delabie, Jan;Smeland, Erlend B.;Ogwang, Martin D.;Reynolds, Steven J.;Fisher, Richard I.;Braziel, Rita M.;Tubbs, Raymond R.;Cook, James R.;Weisenburger, Dennis D.;Chan, Wing C.;Pittaluga, Stefania;Wilson, Wyndham;Waldmann, Thomas A.;Rowe, Martin;Mbulaiteye, Sam M.;Rickinson, Alan B.;Staudt, Louis M.
伯基特淋巴瘤（BL）通常可以通过强化化疗治愈，但这种治疗的毒性使其无法用于发展中国家的老年人和地方性BL患者，因此需要新的策略。我们使用高通量RNA测序和RNA干扰筛选来发现与这种癌症的定义癌基因MYC合作的重要调控途径。在38%的散发性BL（sBL）病例中，致癌CCND3突变产生高度稳定的细胞周期蛋白D3亚型，驱动细胞周期进程。在70%的sBL病例中，影响转录因子TCF 3（E2A）或其负调节因子ID3的突变促进了TCF 3依赖性。TCF 3激活BL中促存活PI（3）激酶通路，部分是通过增强组成型B细胞受体信号传导。这些研究结果表明有机会改善BL患者的治疗。
Burkitt lymphoma (BL) can often be cured by intensive chemotherapy, but the toxicity of such therapy precludes its use in the elderly and in patients with endemic BL in developing countries, necessitating new strategies. We used high throughput RNA sequencing and RNA interference screening to discover essential regulatory pathways that cooperate with MYC, the defining oncogene of this cancer. In 38% of sporadic BL (sBL) cases, oncogenic CCND3 mutations produced highly stable cyclin D3 isoforms that drive cell cycle progression. In 70% of sBL cases, mutations affecting the transcription factor TCF3 (E2A) or its negative regulator ID3 fostered TCF3 dependency. TCF3 activated the pro-survival PI(3) kinase pathway in BL, in part by augmenting constitutive B cell receptor signaling. These findings suggest opportunities to improve therapy for patients with BL.
登录
查看更多内容
影响因子：
3.2
作者：
Yustein, Jason T.;Dang, Chi V.
通讯作者：
Dang, Chi V.
影响因子：
158.5
作者：
Dave, Sandeep S.;Fu, Kai;Staudt, Louis M.
通讯作者：
Staudt, Louis M.
影响因子：
30.5
作者：
Xiao, Changchun;Srinivasan, Lakshmi;Rajewsky, Klaus
通讯作者：
Rajewsky, Klaus
影响因子：
5.3
作者：
PESCE, S;BENEZRA, R
通讯作者：
BENEZRA, R
影响因子：
64.5
作者：
MURRE, C;MCCAW, PS;BALTIMORE, D
通讯作者：
BALTIMORE, D