{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T15:41:01Z","timestamp":1791042061724,"version":"4.1.0"},"reference-count":45,"publisher":"National Academy of Sciences","issue":"1","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2005,1,4]]},"abstract":"<jats:p>Burkitt's lymphoma (BL) is an aggressive B cell neoplasm, which is one of the most common neoplasms of childhood. It is highly widespread in East Africa, where it appears in endemic form associated with Epstein\u2013Barr virus (EBV) infection, and around the world in a sporadic form in which EBV infection is much less common. In addition to being the first human neoplasm to be associated with EBV, BL is associated with a characteristic translocation, in which the Ig promoter is translocated to constitutively activate the c-myc oncogene. Although many BLs respond well to chemotherapy, a significant fraction fails to respond to therapy, leading to death. In this article, we demonstrate that EBV-positive BL expresses high levels of activated mitogen-activated protein kinase and reactive oxygen species (ROS), and that ROS directly regulate NF-\u03baB activation. EBV-negative BLs exhibit activation of phosphoinositol 3-kinase, but do not have elevated levels of ROS. Elevated reactive oxygen may play a role in diverse forms of viral carcinogenesis in humans, including cancers caused by EBV, hepatitis B, C, and human T cell lymphotropic virus. Our findings imply that inhibition of ROS may be useful in the treatment of EBV-induced neoplasia.<\/jats:p>","DOI":"10.1073\/pnas.0408381102","type":"journal-article","created":{"date-parts":[[2004,12,20]],"date-time":"2004-12-20T20:25:38Z","timestamp":1103574338000},"page":"175-179","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":136,"title":["Reactive oxygen signaling and MAPK activation distinguish Epstein\u2013Barr Virus (EBV)-positive versus EBV-negative Burkitt's lymphoma"],"prefix":"10.1073","volume":"102","author":[{"given":"Francesca","family":"Cerimele","sequence":"first","affiliation":[{"name":"Departments of Dermatology, Hematology\/Oncology, and Pathology, Emory University School of Medicine, Atlanta, GA 30322; Department of Microbiology and Immunology, Louisiana State University Health Sciences Center, Shreveport, LA 71130; Cancer Research UK Institute for Cancer Studies, University of Birmingham Medical School, Birmingham B15 2TT, United Kingdom; 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Department of Microbiology and Immunology, Louisiana State University Health Sciences Center, Shreveport, LA 71130; Cancer Research UK Institute for Cancer Studies, University of Birmingham Medical School, Birmingham B15 2TT, United Kingdom; Division of Adult Oncology, Dana\u2013Farber Cancer Institute, Harvard Medical School, Boston, MA 02115; and Whitehead Institute for Biomedical..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Frank","sequence":"additional","affiliation":[{"name":"Departments of Dermatology, Hematology\/Oncology, and Pathology, Emory University School of Medicine, Atlanta, GA 30322; Department of Microbiology and Immunology, Louisiana State University Health Sciences Center, Shreveport, LA 71130; Cancer Research UK Institute for Cancer Studies, University of Birmingham Medical School, Birmingham B15 2TT, United Kingdom; Division of Adult Oncology, Dana\u2013Farber Cancer Institute, Harvard Medical School, Boston, MA 02115; and Whitehead Institute for Biomedical..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Murad","sequence":"additional","affiliation":[{"name":"Departments of Dermatology, Hematology\/Oncology, and Pathology, Emory University School of Medicine, Atlanta, GA 30322; 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