酪氨酸激酶2缺失不影响V617F诱导的小鼠骨髓增殖性肿瘤的严重程度。

Loss of Tyrosine Kinase 2 Does Not Affect the Severity of V617F-induced Murine Myeloproliferative Neoplasm.

作者信息

Yamaji Takumi, Shide Kotaro, Kameda Takuro, Sekine Masaaki, Kamiunten Ayako, Hidaka Tomonori, Kubuki Yoko, Shimoda Haruko, Abe Hiroo, Miike Tadashi, Iwakiri Hisayoshi, Tahara Yoshihiro, Sueta Mitsue, Yamamoto Shojiro, Hasuike Satoru, Nagata Kenji, Shimoda Kazuya

机构信息

Department of Gastroenterology and Hematology, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.

Department of Gastroenterology and Hematology, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan

出版信息

Anticancer Res. 2017 Jul;37(7):3841-3847. doi: 10.21873/anticanres.11763.

DOI:10.21873/anticanres.11763

PMID: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 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.

摘要

背景/目的：在骨髓增殖性肿瘤（MPN）中，Janus激酶2（JAK2）可通过包括JAK2V617F（JAK2VF）在内的突变被激活。目前尚不清楚除JAK2之外的JAK激酶[即JAK1、JAK2、JAK3或酪氨酸激酶2（TYK2）]是否具有协同作用，如增强或抑制JAK2。如果其他激酶增强激活作用，共同靶向它们的疗法可能具有治疗效果。我们研究了TYK2在Jak2VF诱导的小鼠MPN中的作用。