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Blood, 15 June 2008, Vol. 111, No. 12, pp. 5663-5671. Prepublished online as a Blood First Edition Paper on November 5, 2007; DOI 10.1182/blood-2007-04-083402. This Article Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2007-04-083402v1 111/12/5663    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Hexner, E. O Articles by Dobrzanski, P. Search for Related Content PubMed PubMed Citation Articles by Hexner, E. O Articles by Dobrzanski, P. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted April 4, 2007 Accepted September 15, 2007 Lestaurtinib (CEP701)is a JAK2 inhibitor that suppresses JAK2/STAT5 signaling and the proliferation of primary erythroid cells from patients with myeloproliferative disorders Elizabeth O Hexner, Cynthia Serdikoff, Mahfuza Jan, Cezary R. Swider, Candy Robinson, Shi Yang, Thelma Angeles, Stephen G. Emerson, Martin Carroll, Bruce Ruggeri, and Pawel Dobrzanski* Division of Hematology and Oncology, University of Pennsylvania, Philadelphia, PA, United States Division of Oncology, Cephalon, Inc., West Chester, PA, United States * Corresponding author; email: pdobrzan{at}cephalon.com. Recent studies have demonstrated that patients with myeloproliferative disorders (MPDs) frequently have acquired activating mutations in the JAK2 tyrosine kinase. A multikinase screen determined that lestaurtinib (formerly known as CEP-701) inhibits wild type JAK2 kinase activity with an IC50 of 1 nM in vitro. We hypothesized that lestaurtinib would inhibit mutant JAK2 kinase activity and suppress the growth of cells from patients with MPDs. We found that lestaurtinib inhibits the growth of HEL92.1.7 cells which are dependent on mutant JAK2 activity for growth in vitro and in xenograft models. Erythroid cells expanded from primary CD34+ cells from patients with MPDs were inhibited by lestaurtinib at concentrations of 100 nM in 15 of 18 subjects, with concomitant inhibition of phosphorylation of STAT5 and other downstream effectors of JAK2. By contrast, growth of erythroid cells derived from 3 normal controls was not significantly inhibited. These results demonstrate that lestaurtinib, in clinically achievable concentrations, inhibits proliferation and JAK2/STAT5 signaling in cells from patients with MPDs, and therefore holds promise as a therapeutic agent for patients with these disorders. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Can we control JAK? Radek C. Skoda Blood 2008 111: 5419-5420. [Full Text] [PDF] This article has been cited by other articles: L. A. Byers, B. Sen, B. Saigal, L. Diao, J. Wang, M. Nanjundan, T. Cascone, G. B. Mills, J. V. Heymach, and F. M. Johnson Reciprocal Regulation of c-Src and STAT3 in Non-Small Cell Lung Cancer Clin. Cancer Res., November 15, 2009; 15(22): 6852 - 6861. [Abstract] [Full Text] [PDF] P. C.C. Liu, E. Caulder, J. Li, P. Waeltz, A. Margulis, R. Wynn, M. Becker-Pasha, Y. Li, E. Crowgey, G. Hollis, et al. 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