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Alterations in the Rho pathway contribute to Epstein-Barr virus-induced lymphomagenesis in immunosuppressed environments
Cited 8 time in
Web of Science
Cited 8 time in Scopus
- Authors
- Issue Date
- 2018-04
- Publisher
- American Society of Hematology
- Citation
- Blood, Vol.131 No.17, pp.1931-1941
- 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 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.
- ISSN
- 0006-4971
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