RT Journal Article
SR Electronic
T1 JQ1 reduces Epstein-Barr virus-associated lymphoproliferative disease in mice without sustained oncogene repression
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 152306
DO 10.1101/152306
A1 Amanda He
A1 JJ L. Miranda
YR 2017
UL http://biorxiv.org/content/early/2017/06/19/152306.abstract
AB Small molecule inhibitors of bromodomain and extra-terminal (BET) proteins are seeing increased investigation in clinical trials for treatment of hematological malignancies. These compounds also repress oncogene expression driven by the human Epstein-Barr virus (EBV) in cell culture. We therefore tested the efficacy of the prototypical BET inhibitor JQ1 against a mouse xenograft model of post-transplantation lymphoproliferative disorder. JQ1 potently inhibits growth of lymphoblastoid cell lines (LCLs) in culture at low nM concentrations. Growth of other cell lines with similar EBV type III latency transcription programs is comparably inhibited. JQ1 also slows tumor development of an LCL xenograft in immunocompromised mice, but oncogene repression is not observed in endpoint biopsies. We find reduction of EBV-associated lymphoproliferative disease in an animal model encouraging of further studies.