Ribonucleotide reductase represents a novel therapeutic target in primary effusion lymphoma

Primary effusion lymphoma (PEL) is a highly aggressive B-cell malignancy that is closely associated with one of oncogenic viruses infection, Kaposi's sarcoma-associated herpesvirus (KSHV). PEL prognosis is poor and patients barely survive more than 6 months even following active chemotherapy interventions. There is therefore an urgent need to discover more effective targets for PEL management. We recently found that the ribonucleotide reductase (RR) subunit M2 is potentially regulated by the key oncogenic HGF/c-MET pathway in PEL (Dai et al., Blood. 2015;126(26):2821-31). In the current study, we set to investigate the role of RR in PEL pathogenesis and to evaluate its potential as a therapeutic target. We report that the RR inhibitor 3-AP actively induces PEL cell cycle arrest through inhibiting the activity of the NF-κB pathway. Using a xenograft model, we found that 3-AP effectively suppresses PEL progression in immunodeficient mice. Transcriptome analysis of 3-AP treated PEL cell lines reveals altered cellular genes, most of whose roles in PEL have not yet been reported. Taken together, we propose that RR and its signaling pathway may serve as novel actionable targets for PEL management.