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

89 Citations (Scopus)

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

Fingerprint

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

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, 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.
@article{7252e65dd9b04e0a997d483c1ab0d9b8,
title = "Erlotinib effectively inhibits JAK2V617F activity and polycythemia vera cell growth",
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.",
author = "Zhe Li and Mingjiang Xu and Shu Xing and Ho, {Wanting Tina} and Takefumi Ishii and Qingshan Li and Xueqi Fu and Zhao, {Zhizhuang Joe}",
year = "2007",
month = "1",
day = "9",
doi = "10.1074/jbc.C600277200",
language = "English (US)",
volume = "282",
pages = "3428--3432",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "6",

}

TY - JOUR

T1 - Erlotinib effectively inhibits JAK2V617F activity and polycythemia vera cell growth

AU - Li, Zhe

AU - Xu, Mingjiang

AU - Xing, Shu

AU - Ho, Wanting Tina

AU - Ishii, Takefumi

AU - Li, Qingshan

AU - Fu, Xueqi

AU - Zhao, Zhizhuang Joe

PY - 2007/1/9

Y1 - 2007/1/9

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=33947541141&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33947541141&partnerID=8YFLogxK

U2 - 10.1074/jbc.C600277200

DO - 10.1074/jbc.C600277200

M3 - Article

C2 - 17178722

AN - SCOPUS:33947541141

VL - 282

SP - 3428

EP - 3432

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 6

ER -