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

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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

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Polycythemia Vera
Cell growth
Essential Thrombocythemia
Growth
Cells
Transplants
Myeloproliferative Disorders
Leukemia, Erythroblastic, Acute
Primary Myelofibrosis
Protein-Tyrosine Kinases
Assays
Hematopoietic Stem Cells
Bone
Phosphotransferases
Bone Marrow
Erlotinib Hydrochloride
Phenotype
Cell Line
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Biochemistry

Cite this

Li, Z., Xu, M., Xing, S., Ho, W. T., Ishii, T., Li, Q., ... 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

Erlotinib effectively inhibits JAK2V617F activity and polycythemia vera cell growth. / Li, Zhe; Xu, Mingjiang; Xing, Shu; Ho, Wanting Tina; Ishii, Takefumi; Li, Qingshan; Fu, Xueqi; Zhao, Zhizhuang Joe.

In: Journal of Biological Chemistry, Vol. 282, No. 6, 09.01.2007, p. 3428-3432.

Research output: Contribution to journalArticle

Li, Z, Xu, M, Xing, S, Ho, WT, Ishii, T, Li, Q, Fu, X & Zhao, ZJ 2007, 'Erlotinib effectively inhibits JAK2V617F activity and polycythemia vera cell growth', Journal of Biological Chemistry, vol. 282, no. 6, pp. 3428-3432. https://doi.org/10.1074/jbc.C600277200
Li, Zhe ; Xu, Mingjiang ; Xing, Shu ; Ho, Wanting Tina ; Ishii, Takefumi ; Li, Qingshan ; Fu, Xueqi ; Zhao, Zhizhuang Joe. / Erlotinib effectively inhibits JAK2V617F activity and polycythemia vera cell growth. In: Journal of Biological Chemistry. 2007 ; Vol. 282, No. 6. pp. 3428-3432.
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