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 Roh; Min 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

doi:10.1182/blood-2017-07-797209

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 journal › Article › peer-review

12 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 language	English
Pages (from-to)	1931-1941
Number of pages	11
Journal	Blood
Volume	131
Issue number	17
DOIs	https://doi.org/10.1182/blood-2017-07-797209
State	Published - 26 Apr 2018

Bibliographical note

Publisher Copyright:
© 2018 by The American Society of Hematology.

Access to Document

10.1182/blood-2017-07-797209

Cite this

Cho, S. Y., Sung, C. O., Chae, J., Lee, J., Na, D., Kang, W., Kang, J., Min, S., Lee, A., Kwak, E., Kim, J., Choi, B., Kim, H., Chuang, J. H., Pak, H. K., Park, C. S., Park, S., Ko, Y. H., Lee, D., ... Lee, C. (2018). Alterations in the Rho pathway contribute to Epstein-Barr virus–induced lymphomagenesis in immunosuppressed environments. Blood, 131(17), 1931-1941. https://doi.org/10.1182/blood-2017-07-797209

@article{6628b6f059da4bf7bfaed37a9e01a8ab,

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

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.",

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

note = "Publisher Copyright: {\textcopyright} 2018 by The American Society of Hematology.",

year = "2018",

month = apr,

day = "26",

doi = "10.1182/blood-2017-07-797209",

language = "English",

volume = "131",

pages = "1931--1941",

journal = "Blood",

issn = "0006-4971",

publisher = "Elsevier B.V.",

number = "17",

}

Cho, SY, Sung, CO, Chae, J, Lee, J, Na, D, Kang, W, Kang, J, Min, S, Lee, A, Kwak, E, Kim, J, Choi, B, Kim, H, Chuang, JH, Pak, HK, Park, CS, Park, S, Ko, YH, Lee, D, Roh, J, Cho, MS, Park, S, Ju, YS, Suh, YS, Kong, SH, Lee, HJ, Keck, J, Banchereau, J, Liu, ET, Kim, WH, Park, H, Yang, HK, Kim, JI & Lee, C 2018, 'Alterations in the Rho pathway contribute to Epstein-Barr virus–induced lymphomagenesis in immunosuppressed environments', Blood, vol. 131, no. 17, pp. 1931-1941. https://doi.org/10.1182/blood-2017-07-797209

TY - JOUR

T1 - Alterations in the Rho pathway contribute to Epstein-Barr virus–induced lymphomagenesis in immunosuppressed environments

AU - Cho, Sung Yup

AU - Sung, Chang Ohk

AU - Chae, Jeesoo

AU - Lee, Jieun

AU - Na, Deukchae

AU - Kang, Wonyoung

AU - Kang, Jinjoo

AU - Min, Seoyeon

AU - Lee, Ahra

AU - Kwak, Eunhye

AU - Kim, Jooyoung

AU - Choi, Boram

AU - Kim, Hyunsoo

AU - Chuang, Jeffrey H.

AU - Pak, Hyo Kyung

AU - Park, Chan Sik

AU - Park, Sanghui

AU - Ko, Young Hyeh

AU - Lee, Dakeun

AU - Roh, Jin

AU - Cho, Min Sun

AU - Park, Seongyeol

AU - Ju, Young Seok

AU - Suh, Yun Suhk

AU - Kong, Seong Ho

AU - Lee, Hyuk Joon

AU - Keck, James

AU - Banchereau, Jacques

AU - Liu, Edison T.

AU - Kim, Woo Ho

AU - Park, Hansoo

AU - Yang, Han Kwang

AU - Kim, Jong Il

AU - Lee, Charles

PY - 2018/4/26

Y1 - 2018/4/26

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85047871272&partnerID=8YFLogxK

U2 - 10.1182/blood-2017-07-797209

DO - 10.1182/blood-2017-07-797209

M3 - Article

C2 - 29475961

AN - SCOPUS:85047871272

SN - 0006-4971

VL - 131

SP - 1931

EP - 1941

JO - Blood

JF - Blood

IS - 17

ER -

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

Abstract

Bibliographical note

Access to Document

Fingerprint

Cite this