Kinome profiling of non-Hodgkin lymphoma identifies Tyro3 as a therapeutic target in primary effusion lymphoma.
Proc Natl Acad Sci U S A
; 116(33): 16541-16550, 2019 08 13.
Article
em En
| MEDLINE
| ID: mdl-31346082
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.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Linfoma não Hodgkin
/
Receptores Proteína Tirosina Quinases
/
Proteoma
/
Linfoma de Efusão Primária
/
Terapia de Alvo Molecular
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article