The polycythemia vera-associated Jak2 V617F mutant induces tumorigenesis in nude mice

Miyuki Abe, Megumi Tago, Kenji Tago, Jun Kamishimoto, Eriko Yokota, Yoshiko Sonoda, Tadashi Kasahara

Research output: Contribution to journalArticle

19 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)870-877
Number of pages8
JournalInternational Immunopharmacology
Volume9
Issue number7-8
DOIs
Publication statusPublished - 2009 Jul

Fingerprint

Polycythemia Vera
Nude Mice
Carcinogenesis
Cytokines
Mutation
Injections
Oncogenes
Cell Death
Spleen
Liver
Growth

Keywords

  • Anti-apoptosis
  • Jak2
  • Polycythemia vera (PV)
  • Tumorigenesis
  • V617F

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Pharmacology

Cite this

The polycythemia vera-associated Jak2 V617F mutant induces tumorigenesis in nude mice. / Abe, Miyuki; Tago, Megumi; Tago, Kenji; Kamishimoto, Jun; Yokota, Eriko; Sonoda, Yoshiko; Kasahara, Tadashi.

In: International Immunopharmacology, Vol. 9, No. 7-8, 07.2009, p. 870-877.

Research output: Contribution to journalArticle

Abe, Miyuki ; Tago, Megumi ; Tago, Kenji ; Kamishimoto, Jun ; Yokota, Eriko ; Sonoda, Yoshiko ; Kasahara, Tadashi. / The polycythemia vera-associated Jak2 V617F mutant induces tumorigenesis in nude mice. In: International Immunopharmacology. 2009 ; Vol. 9, No. 7-8. pp. 870-877.
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AU - Sonoda, Yoshiko

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