|
|
Blood, 1 June 2006, Vol. 107, No. 11, pp. 4540-4548.
Prepublished online as a Blood First Edition Paper on February 23, 2006; DOI 10.1182/blood-2005-10-4042.
 Previous Article | Next Article 
Submitted October 11, 2005
Accepted January 26, 2006
Constitutive NF- B and NFAT Activation Leads to Stimulation of The BLyS Survival Pathway in Aggressive B Cell Lymphomas
Lingchen Fu, Yen-Chiu Lin-Lee, Lan V Pham, Archito Tamayo, Linda Youshimura, and Richard J Ford*
Department of Hematopathology, University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA; Program in Cancer BIology, University of Texas Graduate School of Biomedical Sciences at Houston, Houston, Texas, USA
Department of Hematopathology, University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA
* Corresponding author; email: rjford{at}mdanderson.org.
B-lymphocyte stimulator (BLyS), a relatively recently recognized member of the tumor necrosis factor ligand family (TNF), is a potent cell survival factor expressed in many hematopoietic cells. BLyS binds to three TNF-R receptors, TACI, BCMA, BAFF-R, to regulate B cell survival, differentiation, and proliferation. The mechanisms involved in BLyS gene expression and regulation are still incompletely understood. In this study, we examined BLyS gene expression, function, and regulation in B cell non-Hodgkin's lymphoma (NHL-B) cells. Our studies indicate that BLyS is constitutively expressed in aggressive NHL-B cells including large B cell lymphoma (LBCL) and mantle cell lymphoma (MCL), playing an important role in the survival and proliferation of malignant B cells. We found that two important transcription factors, NF- B and NFAT, are involved in regulating BLyS expression through at least one NF-B and two NFAT binding sites in the BLyS promoter. We also provide evidence suggesting that the constitutive activation of NF-B and BLyS in NHL-B cells forms a positive feedback loop associated with lymphoma cell survival and proliferation. Our findings indicate that constitutive NF-B and NFAT activations are crucial transcriptional regulators of the BLyS survival pathway in malignant B cells, that could be therapeutic targets in aggressive NHL-B.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
C. R. Fraser, W. Wang, M. Gomez, T. Zhang, S. Mathew, R. R. Furman, D. M. Knowles, A. Orazi, and W. Tam
Transformation of Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma to Interdigitating Dendritic Cell Sarcoma: Evidence for Transdifferentiation of the Lymphoma Clone
Am J Clin Pathol,
December 1, 2009;
132(6):
928 - 939.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. W. Tusche, L. A. Ward, F. Vu, D. McCarthy, M. Quintela-Fandino, J. Ruland, J. L. Gommerman, and T. W. Mak
Differential requirement of MALT1 for BAFF-induced outcomes in B cell subsets
J. Exp. Med.,
November 23, 2009;
206(12):
2671 - 2683.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. S. Kim, J.-Y. Park, I. Jou, and S. M. Park
Functional implication of BAFF synthesis and release in gangliosides-stimulated microglia
J. Leukoc. Biol.,
August 1, 2009;
86(2):
349 - 359.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. J. Novak, S. L. Slager, Z. S. Fredericksen, A. H. Wang, M. M. Manske, S. Ziesmer, M. Liebow, W. R. Macon, S. R. Dillon, T. E. Witzig, et al.
Genetic Variation in B-Cell-Activating Factor Is Associated with an Increased Risk of Developing B-Cell Non-Hodgkin Lymphoma
Cancer Res.,
May 15, 2009;
69(10):
4217 - 4224.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Fu, Y.-C. Lin-Lee, L. V. Pham, A. T. Tamayo, L. C. Yoshimura, and R. J. Ford
BAFF-R promotes cell proliferation and survival through interaction with IKK{beta} and NF-{kappa}B/c-Rel in the nucleus of normal and neoplastic B-lymphoid cells
Blood,
May 7, 2009;
113(19):
4627 - 4636.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D-A Landau, M Rosenzwajg, D Saadoun, D Klatzmann, and P Cacoub
The B lymphocyte stimulator receptor-ligand system in hepatitis C virus-induced B cell clonal disorders
Ann Rheum Dis,
March 1, 2009;
68(3):
337 - 344.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. K. Robbs, A. L. S. Cruz, M. B. F. Werneck, G. P. Mognol, and J. P. B. Viola
Dual Roles for NFAT Transcription Factor Genes as Oncogenes and Tumor Suppressors
Mol. Cell. Biol.,
December 1, 2008;
28(23):
7168 - 7181.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S.-H. Kuo, P.-Y. Yeh, L.-T. Chen, M.-S. Wu, C.-W. Lin, K.-H. Yeh, Y.-S. Tzeng, J.-Y. Chen, P.-N. Hsu, J.-T. Lin, et al.
Overexpression of B cell-activating factor of TNF family (BAFF) is associated with Helicobacter pylori-independent growth of gastric diffuse large B-cell lymphoma with histologic evidence of MALT lymphoma
Blood,
October 1, 2008;
112(7):
2927 - 2934.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. C. Nossent, S. Lester, D. Zahra, C. R. Mackay, and M. Rischmueller
Polymorphism in the 5' regulatory region of the B-lymphocyte activating factor gene is associated with the Ro/La autoantibody response and serum BAFF levels in primary Sjogren's syndrome
Rheumatology,
September 1, 2008;
47(9):
1311 - 1316.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H.-A Kim, S.-H. Jeon, G.-Y. Seo, J.-B. Park, and P.-H. Kim
TGF-{beta}1 and IFN-{gamma} stimulate mouse macrophages to express BAFF via different signaling pathways
J. Leukoc. Biol.,
June 1, 2008;
83(6):
1431 - 1439.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Q. Shen, J. J. Rahn, J. Zhang, N. Gunasekera, X. Sun, A. R.E. Shaw, M. J. Hendzel, P. Hoffman, A. Bernier, and J. C. Hugh
MUC1 Initiates Src-CrkL-Rac1/Cdc42-Mediated Actin Cytoskeletal Protrusive Motility after Ligating Intercellular Adhesion Molecule-1
Mol. Cancer Res.,
April 1, 2008;
6(4):
555 - 567.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. J. Brown, S. L. Ashe, E. Leich, C. Burek, S. Barrans, J. A. Fenton, A. S. Jack, K. Pulford, A. Rosenwald, and A. H. Banham
Potentially oncogenic B-cell activation-induced smaller isoforms of FOXP1 are highly expressed in the activated B cell-like subtype of DLBCL
Blood,
March 1, 2008;
111(5):
2816 - 2824.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. V. Pham, H.-J. Zhou, Y.-C. Lin-Lee, A. T. Tamayo, L. C. Yoshimura, L. Fu, B. G. Darnay, and R. J. Ford
Nuclear Tumor Necrosis Factor Receptor-associated Factor 6 in Lymphoid Cells Negatively Regulates c-Myb-mediated Transactivation through Small Ubiquitin-related Modifier-1 Modification
J. Biol. Chem.,
February 22, 2008;
283(8):
5081 - 5089.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S.-W. Kim, D. W. Oleksyn, R. M. Rossi, C. T. Jordan, I. Sanz, L. Chen, and J. Zhao
Protein kinase C-associated kinase is required for NF-{kappa}B signaling and survival in diffuse large B-cell lymphoma cells
Blood,
February 1, 2008;
111(3):
1644 - 1653.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H.-J. Zhou, L. V. Pham, A. T. Tamayo, Y.-C. Lin-Lee, L. Fu, L. C. Yoshimura, and R. J. Ford
Nuclear CD40 interacts with c-Rel and enhances proliferation in aggressive B-cell lymphoma
Blood,
September 15, 2007;
110(6):
2121 - 2127.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. J. Ford, L. Shen, Y. C. Lin-Lee, L. V. Pham, A. Multani, H.-J. Zhou, A. T. Tamayo, C. Zhang, L. Hawthorn, J. K. Cowell, et al.
Development of a murine model for blastoid variant mantle-cell lymphoma
Blood,
June 1, 2007;
109(11):
4899 - 4906.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Chiu, W. Xu, B. He, S. R. Dillon, J. A. Gross, E. Sievers, X. Qiao, P. Santini, E. Hyjek, J.-w. Lee, et al.
Hodgkin lymphoma cells express TACI and BCMA receptors and generate survival and proliferation signals in response to BAFF and APRIL
Blood,
January 15, 2007;
109(2):
729 - 739.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. I. Fisher, S. H. Bernstein, B. S. Kahl, B. Djulbegovic, M. J. Robertson, S. de Vos, E. Epner, A. Krishnan, J. P. Leonard, S. Lonial, et al.
Multicenter Phase II Study of Bortezomib in Patients With Relapsed or Refractory Mantle Cell Lymphoma
J. Clin. Oncol.,
October 20, 2006;
24(30):
4867 - 4874.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
