國家衛生研究院 NHRI:Item 3990099045/10214
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    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/10214


    Title: The B-cell-activating factor signalling pathway is associated with Helicobacter pylori independence in gastric mucosa-associated lymphoid tissue lymphoma without t(11;18)(q21;q21)
    Other Titles: B cell-activating factor signalling pathway is associated with H. pylori independence in gastric MALT lymphoma without t(11;18)(q21;q21)
    Authors: Kuo, SH;Tsai, HJ;Lin, CW;Yeh, KH;Lee, HW;Wei, MF;Shun, CT;Wu, MS;Hsu, PN;Chen, LT;Cheng, AL
    Contributors: National Institute of Cancer Research
    Abstract: We previously reported that activation of the B-cell-activating factor (BAFF) pathway upregulates nuclear factor-κB (NF-κB) and induces BCL3 and BCL10 nuclear translocation in Helicobacter pylori (HP)-independent gastric diffuse large B-cell lymphoma (DLBCL) tumours with evidence of mucosa-associated lymphoid tissue (MALT). However, the significance of BAFF expression in HP independence of gastric low-grade MALT lymphomas without t(11;18)(q21;q21) remains unexplored. Sixty-four patients who underwent successful HP eradication for localized HP-positive gastric MALT lymphomas without t(11;18)(q21;q21) were studied. BAFF expression was significantly higher in the HP-independent group than in the HP-dependent group [22/26 (84.6%) versus 8/38 (21.1%); p < 0.001]. Similarly, BAFF receptor (BAFF-R) expression (p = 0.004) and nuclear BCL3 (p = 0.004), BCL10 (p < 0.001), NF-κB (p65) (p = 0.001) and NF-κB (p52) (p = 0.005) expression were closely correlated with the HP independence of these tumours. Moreover, BAFF overexpression was significantly associated with BAFF-R expression and nuclear BCL3, BCL10, NF-κB (p65) and NF-κB (p52) expression. These findings were further validated in an independent cohort, including 40 HP-dependent cases and 18 HP-independent cases of gastric MALT lymphoma without t(11;18)(q21;q21). The biological significance of BAFF signalling in t(11;18)(q21;q21)-negative lymphoma cells was further studied in two types of lymphoma B cell: OCI-Ly3 [non-germinal centre B-cell origin DLBCL without t(11;18)(q21;q21) cell line] and MA-1 [t(14;18)(q32;q21)/IGH-MALT1-positive DLBCL cell line]. In both cell lines, we found that BAFF activated the canonical NF-κB and AKT pathways, and induced the formation of BCL10–BCL3 complexes, which translocated to the nucleus. BCL10 and BCL3 nuclear translocation and NF-κB (p65) transactivation were inhibited by either LY294002 or by silencing BCL3 or BCL10 with small interfering RNA. BAFF also activated non-canonical NF-κB pathways (p52) through tumour necrosis factor receptor-associated factor 3 degradation, NF-κB-inducing kinase accumulation, inhibitor of κB kinase (IKK) α/β phosphorylation and NF-κB p100 processing in both cell lines. Our data indicate that the autocrine BAFF signal transduction pathway contributes to HP independence in gastric MALT lymphomas without the t(11;18)(q21;q21) translocation.
    Date: 2017-02
    Relation: Journal of Pathology. 2017 Feb;241(3):420-433.
    Link to: http://dx.doi.org/10.1002/path.4852
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0022-3417&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000393863900010
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85007492956
    Appears in Collections:[Li-Tzong Chen] Periodical Articles
    [Hui-Jen Tsai] Periodical Articles

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