Alterations in the Rho pathway contribute to Epstein-Barr virus–induced lymphomagenesis in immunosuppressed environments

Sung Yup Cho, Chang Ohk Sung, Jeesoo Chae, Jieun Lee, Deukchae Na, Wonyoung Kang, Jinjoo Kang, Seoyeon Min, Ahra Lee, Eunhye Kwak, Jooyoung Kim, Boram Choi, Hyunsoo Kim, Jeffrey H. Chuang, Hyo Kyung Pak, Chan Sik Park, Sanghui Park, Young Hyeh Ko, Dakeun Lee, Jin RohMin Sun Cho, Seongyeol Park, Young Seok Ju, Yun Suhk Suh, Seong Ho Kong, Hyuk Joon Lee, James Keck, Jacques Banchereau, Edison T. Liu, Woo Ho Kim, Hansoo Park, Han Kwang Yang, Jong Il Kim, Charles Lee

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphomas (EBV1-DLBLs) tend to occur in immunocompromised patients, such as the elderly or those undergoing solid organ transplantation. The pathogenesis and genomic characteristics of EBV1-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 EBV1-DLBLs during the engraftment of gastric adenocarcinomas into immunodeficient mice. An integrated genomic analysis of the human-derived EBV1-DLBLs revealed enrichment of mutations in Rho pathway genes, including RHPN2, and Rho pathway transcriptomic activation. Targeting the Rho pathway using a Rho-associated protein kinase (ROCK) inhibitor, fasudil, markedly decreased tumor growth in EBV1-DLBL patient-derived xenograft (PDX) models. Thus, alterations in the Rho pathway appear to contribute to EBV-induced lymphomagenesis in immunosuppressed environments.

Original languageEnglish
Pages (from-to)1931-1941
Number of pages11
JournalBlood
Volume131
Issue number17
DOIs
StatePublished - 26 Apr 2018

Fingerprint

Dive into the research topics of 'Alterations in the Rho pathway contribute to Epstein-Barr virus–induced lymphomagenesis in immunosuppressed environments'. Together they form a unique fingerprint.

Cite this