biostudies-literatureSakamoto Tthe Japan Society for the Promotion of Science71https://www.ebi.ac.uk/biostudies/studies/S-EPMC9862866biostudies-literatureUnknown23(1)Chronic infection with Kaposi's sarcoma-associated herpes virus (KSHV) in B lymphocytes causes primary effusion lymphoma (PEL), the most aggressive form of KSHV-related cancer, which is resistant to conventional chemotherapy. In this study, we report that the BCBL-1 KSHV⁺ PEL cell line does not harbor oncogenic mutations responsible for its aggressive malignancy. Assuming that KSHV viral oncogenes play crucial roles in PEL proliferation, we examined the effect of cyclin-dependent kinase 9 (CDK9) inhibitor FIT-039 on KSHV viral gene expression and KSHV⁺ PEL proliferation. We found that FIT-039 treatment impaired the proliferation of KSHV⁺ PEL cells and the expression of KSHV viral genes in vitro. The effects of FIT-039 treatment on PEL cells were further evaluated in the PEL xenograft model that retains a more physiological environment for the growth of PEL growth and KSHV propagation, and we confirmed that FIT-039 administration drastically inhibited PEL growth in vivo. Our current study indicates that FIT-039 is a potential new anticancer drug targeting KSHV for PEL patients.BMC cancerApplication of the CDK9 inhibitor FIT-039 for the treatment of KSHV-associated malignancy.PMC986286615H05721Ueda KAjiro MHagiwara MWatanabe AMatsushima SSakamoto TfalseApplication of the CDK9 inhibitor FIT-039 for the treatment of KSHV-associated malignancy.Chronic infection with Kaposi's sarcoma-associated herpes virus (KSHV) in B lymphocytes causes primary effusion lymphoma (PEL), the most aggressive form of KSHV-related cancer, which is resistant to conventional chemotherapy. In this study, we report that the BCBL-1 KSHV⁺ PEL cell line does not harbor oncogenic mutations responsible for its aggressive malignancy. Assuming that KSHV viral oncogenes play crucial roles in PEL proliferation, we examined the effect of cyclin-dependent kinase 9 (CDK9) inhibitor FIT-039 on KSHV viral gene expression and KSHV⁺ PEL proliferation. We found that FIT-039 treatment impaired the proliferation of KSHV⁺ PEL cells and the expression of KSHV viral genes in vitro. The effects of FIT-039 treatment on PEL cells were further evaluated in the PEL xenograft model that retains a more physiological environment for the growth of PEL growth and KSHV propagation, and we confirmed that FIT-039 administration drastically inhibited PEL growth in vivo. Our current study indicates that FIT-039 is a potential new anticancer drug targeting KSHV for PEL patients.2023-01-01T00:00:00Z2023 Jan2025-04-22T08:49:19.197Z2024-11-19T19:09:17.735ZS-EPMC98628663667040510.1186/s12885-023-10540-y