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

91 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
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Erlotinib effectively inhibits JAK2<sup>V617F</sup> activity and polycythemia vera cell growth'. Together they form a unique fingerprint.

  • Cite this