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Blood, 15 April 2004, Vol. 103, No. 8, pp. 2879-2891. Prepublished online as a Blood First Edition Paper on November 20, 2003; DOI 10.1182/blood-2003-06-1824. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-06-1824v1 103/8/2879    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Gotlib, J. Articles by Coutré, S. E. Search for Related Content PubMed PubMed Citation Articles by Gotlib, J. Articles by Coutré, S. E. Related Collections Apoptosis Oncogenes and Tumor Suppressors Signal Transduction Review Articles Clinical Trials and Observations Related Letter in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  REVIEW ARTICLES The FIP1L1-PDGFR fusion tyrosine kinase in hypereosinophilic syndrome and chronic eosinophilic leukemia: implications for diagnosis, classification, and management Jason Gotlib, Jan Cools, James M. Malone, III, Stanley L. Schrier, D. Gary Gilliland, and Steven E. Coutré From the Division of Hematology, Department of Internal Medicine, Stanford University School of Medicine, Stanford, CA; Division of Hematology, Department of Medicine, Brigham and Women's Hospital, Boston, MA; and Howard Hughes Medical Institute, Harvard Medical School, Boston, MA. Idiopathic hypereosinophilic syndrome (HES) and chronic eosinophilic leukemia (CEL) comprise a spectrum of indolent to aggressive diseases characterized by unexplained, persistent hypereosinophilia. These disorders have eluded a unique molecular explanation, and therapy has primarily been oriented toward palliation of symptoms related to organ involvement. Recent reports indicate that HES and CEL are imatinib-responsive malignancies, with rapid and complete hematologic remissions observed at lower doses than used in chronic myelogenous leukemia (CML). These BCR-ABL–negative cases lack activating mutations or abnormal fusions involving other known target genes of imatinib, implicating a novel tyrosine kinase in their pathogenesis. A bedside-to-benchtop translational research effort led to the identification of a constitutively activated fusion tyrosine kinase on chromosome 4q12, derived from an interstitial deletion, that fuses the platelet-derived growth factor receptor- gene (PDGFRA) to an uncharacterized human gene FIP1-like-1 (FIP1L1). However, not all HES and CEL patients respond to imatinib, suggesting disease heterogeneity. Furthermore, approximately 40% of responding patients lack the FIP1L1-PDGFRA fusion, suggesting genetic heterogeneity. This review examines the current state of knowledge of HES and CEL and the implications of the FIP1L1-PDGFRA discovery on their diagnosis, classification, and management. (Blood. 2004;103:2879-2891) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Letter in Blood Online: Eosinophilic leukemia and idiopathic hypereosinophilic syndrome are mutually exclusive diagnoses Barbara J. Bain, Jason Gotlib, Jan Cools, James M. Malone, Stanley L. Schrier, D. Gary Gilliland, and Steven E. Coutré Blood 2004 104: 3836-3837. [Full Text] [PDF] This article has been cited by other articles: S. Verstovsek, A. Tefferi, J. Cortes, S. O'Brien, G. Garcia-Manero, A. Pardanani, C. Akin, S. Faderl, T. Manshouri, D. Thomas, et al. Phase II Study of Dasatinib in Philadelphia Chromosome-Negative Acute and Chronic Myeloid Diseases, Including Systemic Mastocytosis Clin. Cancer Res., June 15, 2008; 14(12): 3906 - 3915. [Abstract] [Full Text] [PDF] C. Nishioka, T. Ikezoe, J. Yang, A. Miwa, T. Tasaka, Y. Kuwayama, K. Togitani, H. P. Koeffler, and A. Yokoyama Ki11502, a novel multitargeted receptor tyrosine kinase inhibitor, induces growth arrest and apoptosis of human leukemia cells in vitro and in vivo Blood, May 15, 2008; 111(10): 5086 - 5092. [Abstract] [Full Text] [PDF] M. Puttini, S. Redaelli, L. Moretti, S. Brussolo, R. H Gunby, L. Mologni, E. Marchesi, L. Cleris, A. Donella-Deana, P. Drueckes, et al. 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