Erlotinib effectively inhibits JAK2V617F activity and polycythemia vera cell growth

Zhe Li, Mingjiang Xu, Shu Xing, Wanting Tina Ho, Takefumi Ishii, Qingshan Li, Xueqi Fu, Zhizhuang Joe Zhao

Research output: Contribution to journalArticle

90 Scopus citations

Abstract

JAK2V617F, a mutant of tyrosine kinase JAK2, is found in most patients with polycythemia vera (PV) and a substantial proportion of patients with idiopathic myelofibrosis or essential thrombocythemia. The JAK2 mutant displays a much increased kinase activity and generates a PV-like phenotype in mouse bone marrow transplant models. This study shows that the anticancer drug erlotinib (Tarceva™) is a potent inhibitor of JAK2V617F activity. In vitro colony culture assays revealed that erlotinib at micro-molar concentrations effectively suppresses the growth and expansion of PV hematopoietic progenitor cells while having little effect on normal cells. Furthermore, JAK2V617F-positive cells from PV patients show greater susceptibility to the inhibitor than their negative counterparts. Similar inhibitory effects were found with the JAK2V617F-positive human erythroleukemia HEL cell line. These data suggest that erlotinib may be used for treatment of JAK2V617F-positive PV and other myeloproliferative disorders.

Original languageEnglish (US)
Pages (from-to)3428-3432
Number of pages5
JournalJournal of Biological Chemistry
Volume282
Issue number6
DOIs
StatePublished - Jan 9 2007

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Li, Z., Xu, M., Xing, S., Ho, W. T., Ishii, T., Li, Q., Fu, X., & Zhao, Z. J. (2007). Erlotinib effectively inhibits JAK2V617F activity and polycythemia vera cell growth. Journal of Biological Chemistry, 282(6), 3428-3432. https://doi.org/10.1074/jbc.C600277200