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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 (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 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 Coutre, S. E Search for Related Content PubMed PubMed Citation Articles by Gotlib, J. Articles by Coutre, S. E Related Collections Related Letter in Blood Online Social Bookmarking                   What's this? Submitted June 11, 2003 Accepted November 5, 2003 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, Stanley L Schrier, D Gary Gilliland, and Steven E Coutre Department of Medicine, Division of Hematology, Stanford University School of Medicine, Stanford, CA, USA Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA Howard Hughes Medical Institute, Boston, MA, USA * Corresponding author; email: jason.gotlib{at}stanford.edu or gatsby22@aol.com. 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, which 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. 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. 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