Synergy between PI3K Signaling and MYC in Burkitt Lymphomagenesis

被引：244

作者：

Sander, Sandrine ^{[1
,2
,3
]}

Calado, Dinis P. ^{[1
,2
,3
]}

Srinivasan, Lakshmi ^{[1
,2
]}

Koechert, Karl ^{[3
]}

Zhang, Baochun ^{[1
,2
]}

Rosolowski, Maciej ^{[4
]}

Rodig, Scott J. ^{[5
]}

Holzmann, Karlheinz ^{[6
]}

Stilgenbauer, Stephan ^{[7
]}

Siebert, Reiner ^{[8
]}

Bullinger, Lars ^{[7
]}

Rajewsky, Klaus ^{[1
,2
,3
]}

机构：

[1] Harvard Univ, Sch Med, Program Cellular & Mol Med, Childrens Hosp, Boston, MA 02115 USA

[2] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA

[3] Max Delbruck Ctr Mol Med, D-13092 Berlin, Germany

[4] Univ Leipzig, Inst Med Informat Stat & Epidemiol, D-04107 Leipzig, Germany

[5] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA

[6] Univ Ulm, Microarray Core Facil, D-89081 Ulm, Germany

[7] Univ Hosp Ulm, Dept Internal Med 3, D-89081 Ulm, Germany

[8] Univ Kiel, Inst Human Genet, Univ Hosp Schleswig Holstein Campus Kiel, D-24105 Kiel, Germany

来源：

CANCER CELL | 2012年 / 22卷 / 02期

基金：

美国国家卫生研究院; 欧洲研究理事会;

关键词：

B-CELL LYMPHOMAS; CYCLIN D3; C-MYC; ACTIVATION; RECEPTOR; PATHOGENESIS; SIGNATURES; MICE; P53;

D O I：

10.1016/j.ccr.2012.06.012

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：167 / 179

页数：13

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