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Erlotinib Effectively Inhibits JAK2V617F Activity and Polycythemia Vera Cell Growth.

JAK2(V617F), 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 anti-cancer drug erlotinib (Tarcevatrade mark) is a potent inhibitor of JAK2(V617F) 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, JAK2(V617F)-positive cells from PV patients show greater susceptibility to the inhibitor than their negative counterparts. Similar inhibitory effects were found with the JAK2(V617F)-positive human erythroleukemia HEL cell line. These data suggest that erlotinib may be used for treatment of JAK2(V617F)-positive PV and other myeloproliferative disorders.[1]

References

  1. Erlotinib Effectively Inhibits JAK2V617F Activity and Polycythemia Vera Cell Growth. Li, Z., Xu, M., Xing, S., Ho, W.T., Ishii, T., Li, Q., Fu, X., Zhao, Z.J. J. Biol. Chem. (2007) [Pubmed]
 
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