Alterations in the Rho pathway contribute to Epstein-Barr virus-induced lymphomagenesis in immunosuppressed environments.
Blood 2018 Feb 23 [Epub ahead of print]
Epstein-Barr virus (EBV)-positive diffuse large B cell lymphomas (EBV+-DLBLs) tend to occur in immunocompromised patients, such as the elderly or those undergoing solid organ transplantation. The pathogenesis and genomic characteristics of EBV+-DLBLs are largely unknown because of the limited availability of human samples and lack of experimental animal models. We observed the development of 25 human EBV+-DLBLs during the engraftment of gastric adenocarcinomas into immunodeficient mice. An integrated genomic analysis of the human-derived EBV+-DLBLs revealed enrichment of mutations in Rho pathway genes, including RHPN2, and Rho pathway transcriptomic activation. Targeting the Rho pathway using a ROCK inhibitor, fasudil, markedly decreased tumor growth in EBV+-DLBL patient-derived xenograft (PDX) models. Thus, alterations in the Rho pathway appear to contribute to EBV-induced lymphomagenesis in immunosuppressed environments. Blood 2018 Feb 23 [Epub ahead of print]
Cho, Sung-Yup; Sung, Chang Ohk; Chae, Jeesoo; Lee, Jieun; Na, Deukchae; Kang, Wonyoung; Kang, Jinjoo; Min, Seoyeon; Lee, Ahra; Kwak, Eunhye; Kim, Jooyoung; Choi, Boram; Kim, Hyunsoo; Chuang, Jeffrey H; Pak, Hyo-Kyung; Park, Chan-Sik; Park, Sanghui; Ko, Young Hyeh; Lee, Dakeun; Roh, Jin; Cho, Min-Sun; Park, Seongyeol; Ju, Young Seok; Suh, Yun-Suhk; Kong, Seong-Ho; Lee, Hyuk-Joon; Keck, James; Banchereau, Jacques; Liu, Edison T; Kim, Woo-Ho; Park, Hansoo; Yang, Han-Kwang; Kim, Jong-Il; and Lee, Charles, "Alterations in the Rho pathway contribute to Epstein-Barr virus-induced lymphomagenesis in immunosuppressed environments." (2018). Faculty Research Ahead of Print. 63.