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However, the significance of BAFF<\/jats:styled-content> expression in HP<\/jats:styled-content> independence of gastric low\u2010grade MALT<\/jats:styled-content> lymphomas without t(11;18)(q21;q21) remains unexplored. Sixty\u2010four patients who underwent successful HP<\/jats:styled-content> eradication for localized HP<\/jats:styled-content>\u2010positive gastric MALT<\/jats:styled-content> lymphomas without t(11;18)(q21;q21) were studied. BAFF<\/jats:styled-content> expression was significantly higher in the HP<\/jats:styled-content>\u2010independent group than in the HP<\/jats:styled-content>\u2010dependent group [22\/26 (84.6%) versus 8\/38 (21.1%); p<\/jats:italic>\u2009<\u20090.001]. Similarly, BAFF<\/jats:styled-content> receptor (BAFF<\/jats:styled-content>\u2010R) expression (p<\/jats:italic>\u2009=\u20090.004) and nuclear BCL3<\/jats:styled-content> (p<\/jats:italic>\u2009=\u20090.004), BCL10<\/jats:styled-content> (p<\/jats:italic>\u2009<\u20090.001), NF\u2010\u03baB<\/jats:styled-content> (p65) (p<\/jats:italic>\u2009=\u20090.001) and NF\u2010\u03baB<\/jats:styled-content> (p52) (p<\/jats:italic>\u2009=\u20090.005) expression were closely correlated with the HP<\/jats:styled-content> independence of these tumours. Moreover, BAFF<\/jats:styled-content> overexpression was significantly associated with BAFF<\/jats:styled-content>\u2010R expression and nuclear BCL3<\/jats:styled-content>, BCL10<\/jats:styled-content>, NF\u2010\u03baB<\/jats:styled-content> (p65) and NF\u2010\u03baB<\/jats:styled-content> (p52) expression. These findings were further validated in an independent cohort, including 40 HP<\/jats:styled-content>\u2010dependent cases and 18 HP<\/jats:styled-content>\u2010independent cases of gastric MALT<\/jats:styled-content> lymphoma without t(11;18)(q21;q21). The biological significance of BAFF<\/jats:styled-content> signalling in t(11;18)(q21;q21)\u2010negative lymphoma cells was further studied in two types of lymphoma B cell: OCI<\/jats:styled-content>\u2010Ly3 [non\u2010germinal centre B\u2010cell origin DLBCL<\/jats:styled-content> without t(11;18)(q21;q21) cell line] and MA<\/jats:styled-content>\u20101 [t(14;18)(q32;q21)\/IGH\u2010MALT1<\/jats:styled-content>\u2010positive DLBCL<\/jats:styled-content> cell line]. In both cell lines, we found that BAFF<\/jats:styled-content> activated the canonical NF\u2010\u03baB<\/jats:styled-content> and AKT<\/jats:styled-content> pathways, and induced the formation of BCL10\u2013BCL3<\/jats:styled-content> complexes, which translocated to the nucleus. BCL10<\/jats:styled-content> and BCL3<\/jats:styled-content> nuclear translocation and NF\u2010\u03baB<\/jats:styled-content> (p65) transactivation were inhibited by either LY294002<\/jats:styled-content> or by silencing BCL3<\/jats:styled-content> or BCL10<\/jats:styled-content> with small interfering RNA<\/jats:styled-content>. BAFF<\/jats:styled-content> also activated non\u2010canonical NF\u2010\u03baB<\/jats:styled-content> pathways (p52) through tumour necrosis factor receptor\u2010associated factor 3 degradation, NF\u2010\u03baB<\/jats:styled-content>\u2010inducing kinase accumulation, inhibitor of \u03baB<\/jats:styled-content> kinase (IKK<\/jats:styled-content>) \u03b1\/\u03b2 phosphorylation and NF\u2010\u03baB<\/jats:styled-content> p100 processing in both cell lines. Our data indicate that the autocrine BAFF<\/jats:styled-content> signal transduction pathway contributes to HP<\/jats:styled-content> independence in gastric MALT<\/jats:styled-content> lymphomas without the t(11;18)(q21;q21) translocation. Copyright \u00a9 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.<\/jats:p>","DOI":"10.1002\/path.4852","type":"journal-article","created":{"date-parts":[[2016,11,22]],"date-time":"2016-11-22T01:23:29Z","timestamp":1479777809000},"page":"420-433","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["The B\u2010cell\u2010activating factor signalling pathway is associated with Helicobacter pylori<\/i> independence in gastric mucosa\u2010associated lymphoid tissue lymphoma without t(11;18)(q21;q21)"],"prefix":"10.1002","volume":"241","author":[{"given":"Sung\u2010Hsin","family":"Kuo","sequence":"first","affiliation":[{"name":"Department of Oncology National Taiwan University Hospital Taipei Taiwan"},{"name":"Department of Internal Medicine National Taiwan University Hospital Taipei Taiwan"},{"name":"National Taiwan University Cancer Center National Taiwan University College of Medicine Taipei Taiwan"},{"name":"Graduate Institute of Oncology National 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