Title
Alterations in the Rho pathway contribute to Epstein-Barr virus-induced lymphomagenesis in immunosuppressed environments.
Document Type
Article
Publication Date
4-26-2018
JAX Source
Blood 2018 Apr 26; 131(17):1931-1941
Volume
131
Issue
17
First Page
1931
Last Page
1941
ISSN
1528-0020
PMID
29475961
DOI
https://doi.org/10.1182/blood-2017-07-797209
Grant
CA034196
Abstract
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 Rho-associated protein kinase (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 Apr 26; 131(17):1931-1941.
Recommended Citation
Cho S,
Sung C,
Chae J,
Lee J,
Na D,
Kang W,
Kang J,
Min S,
Lee A,
Kwak E,
Kim J,
Choi B,
Kim H,
Chuang J,
Pak H,
Park C,
Park S,
Ko Y,
Lee D,
Roh J,
Cho M,
Park S,
Ju Y,
Suh Y,
Kong S,
Lee H,
Keck J,
Banchereau J,
Liu E,
Kim W,
Park H,
Yang H,
Kim J,
Lee C.
Alterations in the Rho pathway contribute to Epstein-Barr virus-induced lymphomagenesis in immunosuppressed environments. Blood 2018 Apr 26; 131(17):1931-1941