Kinome profiling of non-Hodgkin lymphoma identifies Tyro3 as a therapeutic target in primary effusion lymphoma
Year: 2019
Type: article
Abstract: Non-Hodgkin lymphomas (NHLs) make up the majority of lymphoma diagnoses and represent a very diverse set of malignancies. We sought to identify kinases uniquely up-regulated in different NHL subtypes. Using multiplexed inhibitor bead-mass spectrometry (MIB/MS), we found Tyro3 was uniquely up-regulated and important for cell survival in primary effusion lymphoma (PEL), which is a viral lymphoma infected with Kaposi's sarcoma-associated herpesvirus (KSHV). Tyro3 was also highly expressed in PEL cell lines as well as in primary PEL exudates. Based on this discovery, we developed an inhibitor against Tyro3 named UNC3810A, which hindered cell growth in PEL, but not in other NHL subtypes where Tyro3 was not highly expressed. UNC3810A also significantly inhibited tumor progression in a PEL xenograft mouse model that was not seen in a non-PEL NHL model. Taken together, our data suggest Tyro3 is a therapeutic target for PEL.
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Funders: Burroughs Wellcome Fund, Leukemia and Lymphoma Society, National Institutes of Health, U.S. Public Health Service, National Cancer Institute, National Institute of Allergy and Infectious Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill
Awards: G2579308029, G2671694828, G3503792436, G386607036, G5888954722, Role of KSHV Viral Proteins in Signaling and Pathogenesis, G7699855597, G9000006710, G9000157298, G9000158818, G9000330263, Molecular Biology of Viral Diseases Predoctoral Training Grant, Viral Oncogenesis, Latency, and Replication, Cancer Center Support Grant
OpenAlex ID: W2964351569