Subtype-specific addiction of the activated B-cell subset of diffuse large B-cell lymphoma to FOXP1

被引：30

作者：

Dekker, Joseph D. ^{[1
]}

Park, Daechan ^{[1
,2
]}

Shaffer, Arthur L., III ^{[3
]}

Kohlhammer, Holger ^{[3
]}

Deng, Wei ^{[1
]}

Lee, Bum-Kyu ^{[1
]}

Ippolito, Gregory C. ^{[1
,2
]}

Georgiou, George ^{[1
,2
]}

Iyer, Vishwanath R. ^{[1
]}

Staudt, Louis M. ^{[3
]}

Tucker, Haley O. ^{[1
]}

机构：

[1] Univ Texas Austin, Inst Cellular & Mol Biol, Dept Mol Biosci, Austin, TX 78712 USA

[2] Univ Texas Austin, Cockrell Sch Engn, Dept Chem Engn, Austin, TX 78712 USA

[3] NCI, Lymphoid Malignancies Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2016年 / 113卷 / 05期

基金：

美国国家卫生研究院;

关键词：

FOXP1; DLBCL; lymphoma; ESSENTIAL TRANSCRIPTIONAL REGULATOR; GENE-EXPRESSION; MOLECULAR SUBTYPES; DOWN-REGULATION; KAPPA-B; DIFFERENTIATION; SURVIVAL; PROTEIN; PROLIFERATION; MATURATION;

D O I：

10.1073/pnas.1524677113

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

High expression of the forkhead box P1 (FOXP1) transcription factor distinguishes the aggressive activated B cell (ABC) diffuse large B-cell lymphoma (DLBCL) subtype from the better prognosis germinal center B-cell (GCB)-DLBCL subtype and is highly correlated with poor outcomes. A genetic or functional role for FOXP1 in lymphomagenesis, however, remains unknown. Here, we report that sustained FOXP1 expression is vital for ABC-DLBCL cell-line survival. Genome-wide analyses revealed direct and indirect FOXP1 transcriptional enforcement of ABC-DLBCL hallmarks, including the classical NF-kappa B and MYD88 (myeloid differentiation primary response gene 88) pathways. FOXP1 promoted gene expression underlying transition of the GCB cell to the plasmablast-the transient B-cell stage targeted in ABC-DLBCL transformation-by antagonizing pathways distinctive of GCB-DLBCL, including that of the GCB "master regulator," BCL6 (B-cell lymphoma 6). Cell-line derived FOXP1 target genes that were highly correlated with FOXP1 expression in primary DLBCL accurately segregated the corresponding clinical subtypes of a large cohort of primary DLBCL isolates and identified conserved pathways associated with ABC-DLBCL pathology.

引用

页码：E577 / E586

页数：10

共 54 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]

MEME SUITE: tools for motif discovery and searching [J].

Bailey, Timothy L. ;

Boden, Mikael ;

Buske, Fabian A. ;

Frith, Martin ;

Grant, Charles E. ;

Clementi, Luca ;

Ren, Jingyuan ;

Li, Wilfred W. ;

Noble, William S. .

NUCLEIC ACIDS RESEARCH, 2009, 37 :W202-W208

[3]

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

[4]

Integrated biochemical and computational approach identifies BCL6 direct target genes controlling multiple pathways in normal germinal center B cells [J].

Basso, Katia ;

Saito, Masumichi ;

Sumazin, Pavel ;

Margolin, Adam A. ;

Wang, Kai ;

Lim, Wei-Keat ;

Kitagawa, Yukiko ;

Schneider, Christof ;

Alvarez, Mariano J. ;

Califano, Andrea ;

Dalla-Favera, Riccardo .

BLOOD, 2010, 115 (05) :975-984

[5]

Potentially oncogenic B-cell activation-induced smaller isoforms of FOXP1 are highly expressed in the activated B cell-like subtype of DLBCL [J].

Brown, Philip J. ;

Ashe, Sally L. ;

Leich, Ellen ;

Burek, Christof ;

Barrans, Sharon ;

Fenton, James A. ;

Jack, Andrew S. ;

Pulford, Karen ;

Rosenwald, Andreas ;

Banham, Alison H. .

BLOOD, 2008, 111 (05) :2816-2824

[6]

A Microarray Platform-Independent Classification Tool for Cell of Origin Class Allows Comparative Analysis of Gene Expression in Diffuse Large B-cell Lymphoma [J].

Care, Matthew A. ;

Barrans, Sharon ;

Worrillow, Lisa ;

Jack, Andrew ;

Westhead, David R. ;

Tooze, Reuben M. .

PLOS ONE, 2013, 8 (02)

[7]

The transcription factors IRF8 and PU.1 negatively regulate plasma cell differentiation [J].

Carotta, Sebastian ;

Willis, Simon N. ;

Hasbold, Jhagvaral ;

Inouye, Michael ;

Pang, Swee Heng Milon ;

Emslie, Dianne ;

Light, Amanda ;

Chopin, Michael ;

Shi, Wei ;

Wang, Hongsheng ;

Morse, Herbert C., III ;

Tarlinton, David M. ;

Corcoran, Lynn M. ;

Hodgkin, Philip D. ;

Nutt, Stephen L. .

JOURNAL OF EXPERIMENTAL MEDICINE, 2014, 211 (11) :2169-2181

[8]

The BCL6 transcriptional program features repression of multiple oncogenes in primary B cells and is deregulated in DLBCL [J].

Ci, Weimin ;

Polo, Jose M. ;

Cerchietti, Leandro ;

Shaknovich, Rita ;

Wang, Ling ;

Yang, Shao Ning ;

Ye, Kenny ;

Farinha, Pedro ;

Horsman, Douglas E. ;

Gascoyne, Randy D. ;

Elemento, Olivier ;

Melnick, Ari .

BLOOD, 2009, 113 (22) :5536-5548

[9]

Clinicopathologic Characterization of Diffuse-Large-B-Cell Lymphoma with an Associated Serum Monoclonal IgM Component [J].

Cox, M. Christina ;

Di Napoli, Arianna ;

Scarpino, Stefania ;

Salerno, Gerardo ;

Tatarelli, Caterina ;

Talerico, Caterina ;

Lombardi, Mariangela ;

Monarca, Bruno ;

Amadori, Sergio ;

Ruco, Luigi .

PLOS ONE, 2014, 9 (04)

[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

← 1 2 3 4 5 6 →