Loss of Tyrosine Kinase 2 Does Not Affect the Severity of Jak2V617F-induced Murine Myeloproliferative Neoplasm.
Anticancer Res
; 37(7): 3841-3847, 2017 07.
Article
em En
| MEDLINE
| ID: mdl-28668884
ABSTRACT
BACKGROUND/AIM:
In myeloproliferative neoplasms (MPN), Janus kinase 2 (JAK2) is activated by mutations including JAK2V617F (JAK2VF). It is unclear whether JAK kinases [i.e. JAK1, JAK2, JAK3, or tyrosine kinase 2 (TYK2)] other than JAK2 have cooperative actions such as enhancement or suppression of JAK2. If other kinases enhance activation, therapies that co-target them could have a therapeutic efficacy. We examined the role of TYK2 in Jak2VF-induced murine MPN. MATERIALS ANDMETHODS:
We crossed Jak2VF transgenic mice and Tyk2-knockout (Tyk2KO) mice to generate Jak2VF/Tyk2KO mice. The disease severity and treatment effect with a JAK2 inhibitor was compared between Jak2VF and Jak2VF/Tyk2KO mice.RESULTS:
Both types of mice developed MPN, and there were no differences in peripheral blood counts, spleen weight, or survival period. Upon JAK2 inhibitor therapy, both types of mice had equally improved leukocytosis and splenomegaly.CONCLUSION:
TYK2 does not have cooperative effects with JAK2VF upon MPN onset nor in the presence of a JAK2 inhibitor.Palavras-chave
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Janus Quinase 2
/
TYK2 Quinase
/
Mutação
/
Transtornos Mieloproliferativos
Limite:
Animals
Idioma:
En
Revista:
Anticancer Res
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Japão