Abstract
Epstein–Barr virus (EBV) is a ubiquitous oncogenic virus that is associated with B cell lymphomas, including Burkitt lymphoma and Hodgkin lymphoma. Previous studies have shown that the phosphatidylinositol 3‐kinase (PI3K)/Akt pathway is activated in EBV‐associated lymphomas and can be a novel therapeutic target. An oral dual inhibitor of PI3Kγ and PI3Kδ, duvelisib, is in clinical trials for the treatment of lymphoid malignancies. In this study, we evaluated how duvelisib affects the activity of the PI3K/Akt signaling pathway and if it has antitumor effects in EBV‐associated lymphoma cell lines. We found that the PI3K/Akt signaling pathway was activated in most of the B and T cell lymphoma cell lines tested. Additionally, duvelisib treatment inhibited cellular growth in the tested cell lines. Overall, B cell lines were more susceptible to duvelisib than T and NK cell lines in vitro regardless of EBV infection. However, the additional influence of duvelisib on the tumor microenvironment was not assessed. Duvelisib treatment induced both apoptosis and cell cycle arrest in EBV‐positive and ‐negative B cell lines, but not in T cell lines. Furthermore, duvelisib treatment reduced the expression of EBV lytic genes (BZLF1 and gp350/220) in EBV‐positive B cell lines, suggesting that duvelisib suppresses the lytic cycle of EBV induced by B cell receptor signaling. However, duvelisib did not induce a remarkable change in the expression of EBV latent genes. These results may indicate that there is therapeutic potential for duvelisib administration in the treatment of EBV‐associated B cell lymphomas and other B cell malignancies.
Highlights
Epstein–Barr virus (EBV) is the primary agent causing infectious mononucleosis and persists asymptomatically for life in most adults
We found that duvelisib inhibited cell growth in EBV-positive and -negative B cell lines, except in P3HR1, in a dose-d ependent manner (Fig. 1A and B)
We evaluated the antitumor effects of duvelisib on EBV-associated lymphoma cell lines and found that B cell lines appeared to be more susceptible to duvelisib than T and natural killer (NK) cell lines regardless of the presence of EBV
Summary
Epstein–Barr virus (EBV) is the primary agent causing infectious mononucleosis and persists asymptomatically for life in most adults. EBV-PTLD disease results in a type III latency pattern characterized by the expression of all EBV latency- associated proteins. These include the EBV nuclear antigens (EBNA) 1, 2, 3A, 3B, and 3C EBV-positive Burkitt lymphoma is usually characterized by a type I latency pattern and primarily expresses EBNA-1 [1]. Patients with EBV-associated lymphoid malignancies treated with cytotoxic chemotherapy are often refractory to it. Understanding the underlying molecular pathways of EBV-associated lymphoid malignancies is necessary to develop more effective treatment strategies
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
