{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,6]],"date-time":"2026-09-06T08:17:12Z","timestamp":1788682632162,"version":"build-2803163510"},"reference-count":80,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2007,7,11]],"date-time":"2007-07-11T00:00:00Z","timestamp":1184112000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2007,9]]},"abstract":"<jats:p>Epstein\u2013Barr virus (EBV) can infect T lymphocytes and manifests as hemophagocytic lymphohistiocytosis (HLH), a distinct entity of hemophagocytic syndrome (HPS) characterized by fever, hepatosplenomegaly, cytopenia, hypercytokinemia, and systemic macrophage activation with hemophagocytosis. In a substantial percentage of HLH patients, the disease may relapse or progress to T\u2010cell lymphoma in months to years. In the present review, the authors summarize the previous studies on the pathogenesis of HLH and the potential mechanism for the progression of disease from HLH to T\u2010cell lymphoma. The infection of T cells by EBV could activate T cells to secrete proinflammatory cytokines, particularly tumor necrosis factor\u2010\u03b1 (TNF\u2010\u03b1), which subsequently activate macrophages. EBV latent membrane protein\u20101 (LMP\u20101) is the viral product responsible for the activation of the TNF receptor (TNFR) associated factors\/nuclear factor\u2010\u03baB (NF\u2010\u03baB)\/ERK pathway to enhance cytokine secretion mediated through the suppression of the <jats:italic>SAP\/SH2D1A<\/jats:italic> gene. The activation of NF\u2010\u03baB will confer resistance to TNF\u2010\u03b1\u2010induced apoptosis on EBV\u2010infected T cells through the down\u2010regulation of TNFR\u20101. Consistent with <jats:italic>in vitro <\/jats:italic>observations, EBV\u2010associated T or natural killer\/T\u2010cell lymphoma showed constitutive activation of NF\u2010\u03baB, explaining its drug resistance, hypercytokinemia, and poor prognosis. Therefore, similar to other inflammation\u2010associated cancers, HLH provides a unique model to study the mechanism of disease progression from a benign virus\u2010infected disorder (HLH) to T\u2010cell lymphoma. Inhibition of the NF\u2010\u03baB signal pathway should provide a potential target for the treatment of HLH and EBV\u2010associated T\u2010cell lymphoma. (<jats:italic>Cancer Sci<\/jats:italic> 2007; 98: 1281\u20131287)<\/jats:p>","DOI":"10.1111\/j.1349-7006.2007.00549.x","type":"journal-article","created":{"date-parts":[[2007,7,11]],"date-time":"2007-07-11T19:54:53Z","timestamp":1184183693000},"page":"1281-1287","source":"Crossref","is-referenced-by-count":75,"title":["Pathogenesis and mechanism of disease progression from hemophagocytic lymphohistiocytosis to Epstein\u2013Barr virus\u2010associated T\u2010cell lymphoma: Nuclear factor\u2010\u03baB pathway as a potential therapeutic 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