RT Journal Article
SR Electronic
T1 Loss of Tyrosine Kinase 2 Does Not Affect the Severity of <em>Jak2</em>V617F-induced Murine Myeloproliferative Neoplasm
JF Anticancer Research
JO Anticancer Res
FD International Institute of Anticancer Research
SP 3841
OP 3847
VO 37
IS 7
A1 TAKUMI YAMAJI
A1 KOTARO SHIDE
A1 TAKURO KAMEDA
A1 MASAAKI SEKINE
A1 AYAKO KAMIUNTEN
A1 TOMONORI HIDAKA
A1 YOKO KUBUKI
A1 HARUKO SHIMODA
A1 HIROO ABE
A1 TADASHI MIIKE
A1 HISAYOSHI IWAKIRI
A1 YOSHIHIRO TAHARA
A1 MITSUE SUETA
A1 SHOJIRO YAMAMOTO
A1 SATORU HASUIKE
A1 KENJI NAGATA
A1 KAZUYA SHIMODA
YR 2017
UL http://ar.iiarjournals.org/content/37/7/3841.abstract
AB 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 and Methods: 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.