Dasatinib therapy results in decreased B cell proliferation, splenomegaly, and tumor growth in a murine model of lymphoma expressing Myc and Epstein-Barr virus LMP2A.
Antiviral Res
; 95(1): 49-56, 2012 Jul.
Article
em En
| MEDLINE
| ID: mdl-22609829
ABSTRACT
Epstein-Barr virus (EBV) infection and latency has been associated with malignant diseases including nasopharyngeal carcinoma, Hodgkin lymphoma, Burkitt lymphoma, and immune deficiency associated lymphoproliferative diseases. EBV-encoded latent membrane protein 2A (LMP2A) recruits Lyn and Syk kinases via its SH2-domain binding motifs, and modifies their signaling pathways. LMP2A transgenic mice develop hyperproliferative bone marrow B cells and immature peripheral B cells through modulation of Lyn kinase signaling. LMP2A/λ-MYC double transgenic mice develop splenomegaly and cervical lymphomas starting at 8 weeks of age. We reasoned that targeting Lyn in LMP2A-expressing B cells with dasatinib would provide a therapeutic option for EBV-associated malignancies. Here, we show that dasatinib inhibits B cell colony formation by LMP2A transgenic bone marrow cells, and reverses splenomegaly and tumor growth in both a pre-tumor and a syngeneic tumor transfer model of EBV-associated Burkitt lymphoma. Our data support the idea that dasatinib may prove to be an effective therapeutic molecule for the treatment of EBV-associated malignancies.
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
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Tipos_de_cancer
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Outros_tipos
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Tratamento
Base de dados:
MEDLINE
Assunto principal:
Pirimidinas
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Tiazóis
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Linfócitos B
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Proteínas da Matriz Viral
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Proteína Oncogênica p55(v-myc)
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Linfoma de Burkitt
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Proliferação de Células
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Antineoplásicos
Limite:
Animals
Idioma:
En
Revista:
Antiviral Res
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Estados Unidos