Constitutive Canonical NF-κB Activation Cooperates with Disruption of BLIMP1 in the Pathogenesis of Activated B Cell-like Diffuse Large Cell Lymphoma

被引：157

作者：

Calado, Dinis Pedro ^{[1
,2
]}

Zhang, Baochun ^{[1
,2
]}

Srinivasan, Lakshmi ^{[1
,2
]}

Sasaki, Yoshiteru ^{[1
,2
,5
]}

Seagal, Jane ^{[1
,2
]}

Unitt, Christine ^{[3
]}

Rodig, Scott ^{[3
]}

Kutok, Jeffery ^{[3
]}

Tarakhovsky, Alexander ^{[4
]}

Schmidt-Supprian, Marc ^{[1
,2
,6
]}

Rajewsky, Klaus ^{[1
,2
]}

机构：

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

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

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

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

[5] Riken Ctr Dev Biol, Kobe, Hyogo 6500047, Japan

[6] Max Planck Inst Biochem, D-82152 Martinsried, Germany

来源：

CANCER CELL | 2010年 / 18卷 / 06期

关键词：

GENE-EXPRESSION; MOLECULAR SUBTYPES; MULTIPLE-MYELOMA; IN-VIVO; LYMPHOCYTES; MUTATIONS; TRANSCRIPTION; INACTIVATION; SUBGROUPS; PATHWAYS;

D O I：

10.1016/j.ccr.2010.11.024

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Diffuse large B cell lymphoma (DLBCL) comprises disease entities with distinct genetic profiles, including germinal center B cell (GCB)-like and activated B cell (ABC)-like DLBCLs. Major differences between these two subtypes include genetic aberrations leading to constitutive NF-kappa B activation and interference with terminal B cell differentiation through BLIMP1 inactivation, observed in ABC- but not GCB-DLBCL. Using conditional gain-of-function and/or loss-of-function mutagenesis in the mouse, we show that constitutive activation of the canonical NF-kappa B pathway cooperates with disruption of BLIMP1 in the development of a lymphoma that resembles human ABC-DLBCL. Our work suggests that both NE-kappa B signaling, as an oncogenic event, and BLIMP1, as a tumor suppressor, play causal roles in the pathogenesis of ABC-DLBCL.

引用

页码：580 / 589

页数：10

共 37 条

[1] Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling [J].

Alizadeh, AA ;

Eisen, MB ;

Davis, RE ;

Ma, C ;

Lossos, IS ;

Rosenwald, A ;

Boldrick, JG ;

Sabet, H ;

Tran, T ;

Yu, X ;

Powell, JI ;

Yang, LM ;

Marti, GE ;

Moore, T ;

Hudson, J ;

Lu, LS ;

Lewis, DB ;

Tibshirani, R ;

Sherlock, G ;

Chan, WC ;

Greiner, TC ;

Weisenburger, DD ;

Armitage, JO ;

Warnke, R ;

Levy, R ;

Wilson, W ;

Grever, MR ;

Byrd, JC ;

Botstein, D ;

Brown, PO ;

Staudt, LM .

NATURE, 2000, 403 (6769) :503-511

[2] Commitment of B lymphocytes to a plasma cell fate is associated with Blimp-1 expression in vivo [J].

Angelin-Duclos, C ;

Cattoretti, G ;

Lin, KI ;

Calame, K .

JOURNAL OF IMMUNOLOGY, 2000, 165 (10) :5462-5471

[3] Frequent engagement of the classical and alternative NF-κB pathways by diverse genetic abnormalities in multiple myeloma [J].

Annunziata, Christina M. ;

Davis, R. Eric ;

Demchenko, Yulia ;

Bellamy, William ;

Gabrea, Ana ;

Zhan, Fenghuang ;

Lenz, Georg ;

Hanamura, Ichiro ;

Wright, George ;

Xiao, Wenming ;

Dave, Sandeep ;

Hurt, Elaine M. ;

Tan, Bruce ;

Zhao, Hong ;

Stephens, Owen ;

Santra, Madhumita ;

Williams, David R. ;

Dang, Lenny ;

Barlogie, Bart ;

Shaughnessy, John D., Jr. ;

Kuehl, W. Michael ;

Staudt, Louis M. .

CANCER CELL, 2007, 12 (02) :115-130

[4]

[Anonymous], WHO CLASS TUM HAEM L

[5]

Banham AH, 2005, CLIN CANCER RES, V11, P1065

[6] Constitutive CD40L Expression on B Cells Prematurely Terminates Germinal Center Response and Leads to Augmented Plasma Cell Production in T Cell Areas [J].

Bolduc, Anna ;

Long, Eugene ;

Stapler, Dale ;

Cascalho, Marilia ;

Tsubata, Takeshi ;

Koni, Pandelakis A. ;

Shimoda, Michiko .

JOURNAL OF IMMUNOLOGY, 2010, 185 (01) :220-230

[7] Tracking germinal center B cells expressing germ-line immunoglobulin γ1 transcripts by conditional gene targeting [J].

Casola, Stefano ;

Cattoretti, Giorgio ;

Uyttersprot, Nathalie ;

Koralov, Sergei B. ;

Segal, Jane ;

Hao, Zhenyue ;

Waisman, Ari ;

Egert, Angela ;

Ghitza, Dvora ;

Rajewsky, Klaus .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2006, 103 (19) :7396-7401

[8] A New Immunostain Algorithm Classifies Diffuse Large B-Cell Lymphoma into Molecular Subtypes with High Accuracy [J].

Choi, William W. L. ;

Weisenburger, Dennis D. ;

Greiner, Timothy C. ;

Piris, Miguel A. ;

Banham, Alison H. ;

Delabie, Jan ;

Braziel, Rita M. ;

Geng, Huimin ;

Iqbal, Javeed ;

Lenz, Georg ;

Vose, Julie M. ;

Hans, Christine P. ;

Fu, Kai ;

Smith, Lynette M. ;

Li, Min ;

Liu, Zhongfeng ;

Gascoyne, Randy D. ;

Rosenwald, Andreas ;

Ott, German ;

Rimsza, Lisa M. ;

Campo, Elias ;

Jaffe, Elaine S. ;

Jaye, David L. ;

Staudt, Louis M. ;

Chan, Wing C. .

CLINICAL CANCER RESEARCH, 2009, 15 (17) :5494-5502

[9] Mutations of multiple genes cause deregulation of NF-κB in diffuse large B-cell lymphoma [J].

Compagno, Mara ;

Lim, Wei Keat ;

Grunn, Adina ;

Nandula, Subhadra V. ;

Brahmachary, Manisha ;

Shen, Qiong ;

Bertoni, Francesco ;

Ponzoni, Maurilio ;

Scandurra, Marta ;

Califano, Andrea ;

Bhagat, Govind ;

Chadburn, Amy ;

Dalla-Favera, Riccardo ;

Pasqualucci, Laura .

NATURE, 2009, 459 (7247) :717-U124

[10] Chronic active B-cell-receptor signalling in diffuse large B-cell lymphoma [J].

Davis, R. Eric ;

Ngo, Vu N. ;

Lenz, Georg ;

Tolar, Pavel ;

Young, Ryan M. ;

Romesser, Paul B. ;

Kohlhammer, Holger ;

Lamy, Laurence ;

Zhao, Hong ;

Yang, Yandan ;

Xu, Weihong ;

Shaffer, Arthur L. ;

Wright, George ;

Xiao, Wenming ;

Powell, John ;

Jiang, Jian-Kang ;

Thomas, Craig J. ;

Rosenwald, Andreas ;

Ott, German ;

Muller-Hermelink, Hans Konrad ;

Gascoyne, Randy D. ;

Connors, Joseph M. ;

Johnson, Nathalie A. ;

Rimsza, Lisa M. ;

Campo, Elias ;

Jaffe, Elaine S. ;

Wilson, Wyndham H. ;

Delabie, Jan ;

Smeland, Erlend B. ;

Fisher, Richard I. ;

Braziel, Rita M. ;

Tubbs, Raymond R. ;

Cook, J. R. ;

Weisenburger, Dennis D. ;

Chan, Wing C. ;

Pierce, Susan K. ;

Staudt, Louis M. .

NATURE, 2010, 463 (7277) :88-U97

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