Alterations in the Rho pathway contribute to Epstein-Barr virus-induced lymphomagenesis in immunosuppressed environments
- 주제(기타) Hematology
- 설명문(일반) [Cho, Sung-Yup; Na, Deukchae] Ewha Womans Univ, Ewha Inst Convergence Med, Mokdong Hosp, 1071 Anyangcheon Ro, Seoul 07985, South Korea; [Sung, Chang Ohk; Kang, Wonyoung; Kim, Hyunsoo; Chuang, Jeffrey H.; Banchereau, Jacques; Liu, Edison T.; Lee, Charles] Jackson Lab Genom Med, 10 Discovery Dr, Farmington, CT 06032 USA; [Sung, Chang Ohk; Pak, Hyo-Kyung; Park, Chan-Sik; Roh, Jin] Univ Ulsan, Dept Pathol, Asan Med Ctr, Coll Med, Seoul, South Korea; [Chae, Jeesoo; Kim, Jong-Il] Seoul Natl Univ, Dept Biomed Sci, Coll Med, 103 Daehak Ro, Seoul 03080, South Korea; [Lee, Jieun; Kang, Wonyoung; Kang, Jinjoo; Min, Seoyeon; Lee, Ahra; Kwak, Eunhye; Kim, Jooyoung; Choi, Boram] Ewha Womans Univ, Dept Life Sci, Seoul, South Korea; [Pak, Hyo-Kyung] Univ Ulsan, Cell Dysfunct Res Ctr, Coll Med, Seoul, South Korea; [Park, Sanghui; Cho, Min-Sun] Ewha Womans Univ, Dept Pathol, Coll Med, Seoul, South Korea; [Ko, Young Hyeh] Sungkyunkwan Univ, Dept Pathol & Translat Genom, Samsung Med Ctr, Sch Med, Seoul, South Korea; [Lee, Dakeun] Ajou Univ, Dept Pathol, Sch Med, Suwon, South Korea; [Park, Seongyeol; Ju, Young Seok] Korea Adv Inst Sci & Technol, Grad Sch Med Sci & Engn, Daejeon, South Korea; [Suh, Yun-Suhk; Kong, Seong-Ho; Lee, Hyuk-Joon; Yang, Han-Kwang] Seoul Natl Univ, Coll Med, Dept Surg, Seoul, South Korea; [Lee, Hyuk-Joon; Kim, Woo-Ho; Yang, Han-Kwang; Kim, Jong-Il] Seoul Natl Univ, Canc Res Inst, Coll Med, Seoul, South Korea; [Keck, James] Jackson Lab, Sacramento, CA USA; [Kim, Woo-Ho] Seoul Natl Univ, Dept Pathol, Coll Med, Seoul, South Korea; [Park, Hansoo] Gwangju Inst Sci & Technol, Dept Biomed Sci & Engn, Gwangju, South Korea; [Kim, Jong-Il] Seoul Natl Univ, Genom Med Inst, Med Res Ctr, Seoul, South Korea
- 등재 SCIE, SCOPUS
- 발행기관 AMER SOC HEMATOLOGY
- 발행년도 2018
- URI http://www.dcollection.net/handler/ewha/000000151757
- 본문언어 영어
- Published As http://dx.doi.org/10.1182/blood-2017-07-797209
초록/요약
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 ofmutations 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 tumorgrowth inEBV1-DLBL patient-derived xenograft (PDX) models. Thus, alterations in the Rho pathway appear to contribute to EBV-induced lymphomagenesis in immunosuppressed environments.
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