BLIMP1 Is a Tumor Suppressor Gene Frequently Disrupted in Activated B Cell-like Diffuse Large B Cell Lymphoma

被引：269

作者：

Mandelbaum, Jonathan ^{[1
,2
,3
]}

Bhagat, Govind ^{[1
,2
,4
]}

Tang, Hongyan ^{[1
,2
]}

Mo, Tongwei ^{[1
,2
]}

Brahmachary, Manisha ^{[1
,2
]}

Shen, Qiong ^{[1
,2
]}

Chadburn, Amy ^{[2
,6
]}

Rajewsky, Klaus ^{[7
,8
]}

Tarakhovsky, Alexander ^{[9
]}

Pasqualucci, Laura ^{[1
,2
,4
]}

Dalla-Favera, Riccardo ^{[1
,2
,4
,5
]}

机构：

[1] Columbia Univ, Inst Canc Genet, New York, NY 10032 USA

[2] Columbia Univ, Herbert Irving Comprehens Canc Ctr, New York, NY 10032 USA

[3] Columbia Univ, Integrated Program Cellular Mol & Biomed Studies, New York, NY 10032 USA

[4] Columbia Univ, Dept Pathol & Cell Biol, New York, NY 10032 USA

[5] Columbia Univ, Dept Genet & Dev, New York, NY 10032 USA

[6] Cornell Univ, Weill Med Coll, Dept Pathol & Lab Med, New York, NY 10065 USA

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

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

[9] Rockefeller Univ, Lab Lymphocyte Signaling, New York, NY 10065 USA

来源：

CANCER CELL | 2010年 / 18卷 / 06期

关键词：

DEREGULATED BCL6 EXPRESSION; DOWN-REGULATION; PLASMA-CELLS; KAPPA-B; C-MYC; DIFFERENTIATION; TRANSCRIPTION; MUTATIONS; REPRESSION; SUBSET;

D O I：

10.1016/j.ccr.2010.10.030

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

Diffuse large B cell lymphoma (DLBCL) is a heterogeneous disease composed of at least two distinct subtypes: germinal center B cell-like (GCB) and activated B cell-like (ABC) DLBCL. These phenotypic subtypes segregate with largely unique genetic lesions, suggesting the involvement of different pathogenetic mechanisms. In this report we show that the BLIMP1/PRDM1 gene is inactivated by multiple mechanisms, including homozygous deletions, truncating or missense mutations, and transcriptional repression by constitutively active BCL6, in similar to 53% of ABC-DLBCL. In vivo, conditional deletion of Blimp1 in mouse B cells promotes the development of lymphoproliferative disorders recapitulating critical features of the human ABC-DLBCL. These results demonstrate that BLIMP1 is a bona fide tumor-suppressor gene whose loss contributes to lymphomagenesis by blocking plasma cell differentiation.

引用

页码：568 / 579

页数：12

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