title: The polycythemia vera-associated Jak2 V617F mutant induces tumorigenesis in nude mice.
abstract: The somatic Jak2 mutation (V617F) was identified in most patients with polycythemia vera (PV). Here, we show that the activating Jak2 V617F mutant completely protected Ba/F3 cells from cytokine withdrawal-induced apoptotic cell death. Interestingly, Ba/F3 cells expressing Jak2 V617F mutant induced rapid tumorigenesis in nude mice, leading to rapid death. Whereas an injection of Ba/F3 cells expressing wild-type Jak2 had no effect, an injection of Ba/F3 cells expressing Jak2 V617F mutant promptly invaded and spread into various distinct organs, such as the liver and spleen. Strikingly, Jak2 inhibitor, AG490 potently inhibited cytokine-independent cell growth induced by the Jak2 V617F mutant. Also, treatment with AG490 effectively delayed Jak2 V617F mutant-induced tumorigenesis in nude mice. Thus, our results both in vitro and in vivo suggest that Jak2 harboring V617F mutation is a potent oncogene able to promote cell transformation and tumorigenesis.
authors.affiliation: Department of Biochemistry, Faculty of Pharmacology, Keio University, 1-5-30 Shibakoen, Minato-ku, Tokyo 105-8512, Japan.
authors.forename: Miyuki
authors.initials: M
authors.lastname: Abe
authors.forename: Megumi
authors.initials: M
authors.lastname: Funakoshi-Tago
authors.forename: Kenji
authors.initials: K
authors.lastname: Tago
authors.forename: Jun
authors.initials: J
authors.lastname: Kamishimoto
authors.forename: Eriko
authors.initials: E
authors.lastname: Aizu-Yokota
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Sonoda
authors.forename: Tadashi
authors.initials: T
authors.lastname: Kasahara