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Blood, 1 October 2008, Vol. 112, No. 7, pp. 2927-2934.
Prepublished online as a Blood First Edition Paper on July 15, 2008; DOI 10.1182/blood-2008-02-137513.


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Submitted February 5, 2008
Accepted June 22, 2008

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

Sung-Hsin Kuo, Pei -Yen Yeh, Li-Tzong Chen, Ming-Shiang Wu, Chung-Wu Lin, Kun-Huei Yeh, Yi-Shin Tzeng, Jing-Yi Chen, Ping-Ning Hsu, Jaw-Town Lin, and Ann-Lii Cheng*

Department of Oncology, National Taiwan University Hospital, Yun-Lin Branch, Yun-Lin, Taiwan
Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan
Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan
Cancer Research Center, National Taiwan University College of Medicine, Taipei, Taiwan
National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan

* Corresponding author; email: alcheng{at}ntu.edu.tw.

We have recently demonstrated that nuclear expression of BCL10 predicts H. pylori (HP)-independence of early-stage gastric diffuse large B-cell lymphoma with histologic evidence of MALT lymphoma (DLBCL[MALT]). In this study, we examined the role of B-cell activating factor of TNF family (BAFF) in mediating BCL10 nuclear translocation and HP-independence of gastric DLBCL(MALT). We used immunohistochemistry and immunoblotting to measure the expression of BAFF, pAKT, BCL3, BCL10, and NF-{kappa}B. Transactivity of NF-{kappa}B was measured by electromobility shift assay. In lymphoma samples from 26 patients with gastric DLBCL(MALT), we detected aberrant expression of BAFF in 7 of 10 (70.0%) HP-independent and in 3 of 16 (18.8%) HP-dependent cases (P = .015). BAFF overexpression was associated with pAKT expression (P = .032), and nuclear expression of BCL3 (P = .014), BCL10 (P = .015), and NF-{kappa}B (P = .004). In B-cell lymphoma Pfeiffer cells, BAFF activated NF-{kappa}B and AKT; the activated NF-{kappa}B upregulated BCL10, and the activated AKT caused formation of BCL10/BCL3 complexes that translocated to the nucleus. Inhibition of AKT by LY294002 (a PI3K inhibitor) blocked BCL10 nuclear translocation, NF-{kappa}B transactivity, and BAFF expression. Our results indicate that autocrine BAFF signal transduction pathways may contribute to HP-independent growth of gastric DLBCL(MALT).


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Z. Li, H. Wang, L. Xue, D.-M. Shin, D. Roopenian, W. Xu, C.-F. Qi, M. Y. Sangster, C. J. Orihuela, E. Tuomanen, et al.
E{micro}-BCL10 mice exhibit constitutive activation of both canonical and noncanonical NF-{kappa}B pathways generating marginal zone (MZ) B-cell expansion as a precursor to splenic MZ lymphoma
Blood, November 5, 2009; 114(19): 4158 - 4168.
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