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.

Abstract

We have recently demonstrated that nuclear expression of BCL10 predicts Helicobacter pylori (HP) independence of early-stage gastric diffuse large B-cell lymphoma (DLBCL) with histologic evidence of mucosa-associated lymphoid tissue (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-kappaB. Transactivity of NF-kappaB 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%) 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-kappaB (P = .004). In B-cell lymphoma Pfeiffer cells, BAFF activated NF-kappaB and AKT; the activated NF-kappaB up-regulated 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-kappaB transactivity, and BAFF expression. Our results indicate that autocrine BAFF signal transduction pathways may contribute to HP-independent growth of gastric DLBCL (MALT).

• Authors: 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, Ann-Lii Cheng
• Journal: Blood (Blood) Vol. 112 Issue 7 Pg. 2927-34 (Oct 01 2008) ISSN: 1528-0020 [Electronic] United States
• PMID: 18628489 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adaptor Proteins, Signal Transducing
• B-Cell Activating Factor
• B-Cell CLL-Lymphoma 10 Protein
• B-Cell Lymphoma 3 Protein
• BCL10 protein, human
• BCL3 protein, human
• NF-kappa B
• Proto-Oncogene Proteins
• Transcription Factors
• Proto-Oncogene Proteins c-akt

Topics

• Adaptor Proteins, Signal Transducing (metabolism)
• Adult
• Aged
• Aged, 80 and over
• B-Cell Activating Factor (metabolism)
• B-Cell CLL-Lymphoma 10 Protein
• B-Cell Lymphoma 3 Protein
• Cell Line, Tumor
• Cell Nucleus (metabolism)
• Enzyme Activation
• Female
• Helicobacter pylori (physiology)
• Humans
• Lymphoma, B-Cell, Marginal Zone (enzymology, microbiology, pathology)
• Lymphoma, Large B-Cell, Diffuse (enzymology, microbiology, pathology)
• Male
• Middle Aged
• Models, Biological
• NF-kappa B (metabolism)
• Protein Transport
• Proto-Oncogene Proteins (metabolism)
• Proto-Oncogene Proteins c-akt (metabolism)
• Signal Transduction
• Stomach Neoplasms (enzymology, microbiology, pathology)
• Transcription Factors (metabolism)
• Up-Regulation