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Prepublished online as a Blood First Edition Paper on April 3, 2003; DOI 10.1182/blood-2003-01-0006. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-01-0006v1 101/12/4660    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 Klion, A. D. Articles by Nutman, T. B. Search for Related Content PubMed PubMed Citation Articles by Klion, A. D. Articles by Nutman, T. B. Related Collections Neoplasia Phagocytes Plenary Papers Clinical Trials and Observations Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 June 2003, Vol. 101, No. 12, pp. 4660-4666 PLENARY PAPERS Elevated serum tryptase levels identify a subset of patients with a myeloproliferative variant of idiopathic hypereosinophilic syndrome associated with tissue fibrosis, poor prognosis, and imatinib responsiveness Amy D. Klion, Pierre Noel, Cem Akin, Melissa A. Law, D. Gary Gilliland, Jan Cools, Dean D. Metcalfe, and Thomas B. Nutman From the Laboratory of Parasitic Diseases and the Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD; and the Division of Hematology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA. Since serum tryptase levels are elevated in some patients with myeloproliferative disorders, we examined their utility in identifying a subset of patients with hypereosinophilic syndrome (HES) and an underlying myeloproliferative disorder. Elevated serum tryptase levels (> 11.5 ng/mL) were present in 9 of 15 patients with HES and were associated with other markers of myeloproliferation, including elevated B12 levels and splenomegaly. Although bone marrow biopsies in these patients showed increased numbers of CD25+ mast cells and atypical spindle-shaped mast cells, patients with HES and elevated serum tryptase could be distinguished from patients with systemic mastocytosis and eosinophilia by their clinical manifestations, the absence of mast cell aggregates, the lack of a somatic KIT mutation, and the presence of the recently described fusion of the Fip1–like 1 (FIP1L1) gene to the platelet-derived growth factor receptor gene (PDGFRA). Patients with HES and elevated serum tryptase were more likely to develop fibroproliferative end organ damage, and 3 of 9 died within 5 years of diagnosis in contrast to 0 of 6 patients with normal serum tryptase levels. All 6 patients with HES and elevated tryptase treated with imatinib demonstrated a clinical and hematologic response. In summary, elevated serum tryptase appears to be a sensitive marker of a myeloproliferative variant of HES that is characterized by tissue fibrosis, poor prognosis, and imatinib responsiveness. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Major link between mast cells and the idiopathic hypereosinophilic syndrome Marc E. Rothenberg Blood 2003 101: 4647-4648. [Full Text] [PDF] This article has been cited by other articles: I. Lahortiga, C. Akin, J. Cools, T. M. Wilson, N. Mentens, D. C. Arthur, I. Maric, P. Noel, C. Kocabas, P. Marynen, et al. Activity of imatinib in systemic mastocytosis with chronic basophilic leukemia and a PRKG2-PDGFRB fusion Haematologica, January 1, 2008; 93(1): 49 - 56. [Abstract] [Full Text] [PDF] A. Reiter, D. Grimwade, and N. C.P. Cross Diagnostic and therapeutic management of eosinophilia-associated chronic myeloproliferative disorders Haematologica, September 1, 2007; 92(9): 1153 - 1158. [Full Text] [PDF] M. Baccarani, D. Cilloni, M. Rondoni, E. Ottaviani, F. Messa, S. Merante, M. Tiribelli, F. Buccisano, N. Testoni, E. Gottardi, et al. The efficacy of imatinib mesylate in patients with FIP1L1-PDGFR{alpha}-positive hypereosinophilic syndrome. Results of a multicenter prospective study Haematologica, September 1, 2007; 92(9): 1173 - 1179. [Abstract] [Full Text] [PDF] J. V. Jovanovic, J. Score, K. Waghorn, D. Cilloni, E. Gottardi, G. Metzgeroth, P. Erben, H. Popp, C. Walz, A. Hochhaus, et al. Low-dose imatinib mesylate leads to rapid induction of major molecular responses and achievement of complete molecular remission in FIP1L1-PDGFRA positive chronic eosinophilic leukemia Blood, June 1, 2007; 109(11): 4635 - 4640. [Abstract] [Full Text] [PDF] M. Buitenhuis, L. P. Verhagen, J. Cools, and P. J. Coffer Molecular Mechanisms Underlying FIP1L1-PDGFRA-Mediated Myeloproliferation Cancer Res., April 15, 2007; 67(8): 3759 - 3766. [Abstract] [Full Text] [PDF] C. Akin Molecular Diagnosis of Mast Cell Disorders: A Paper from the 2005 William Beaumont Hospital Symposium on Molecular Pathology J. Mol. Diagn., September 1, 2006; 8(4): 412 - 419. [Abstract] [Full Text] [PDF] E. Lierman, C. Folens, E. H. Stover, N. Mentens, H. Van Miegroet, W. Scheers, M. Boogaerts, P. Vandenberghe, P. Marynen, and J. Cools Sorafenib is a potent inhibitor of FIP1L1-PDGFR{alpha} and the imatinib-resistant FIP1L1-PDGFR{alpha} T674I mutant Blood, August 15, 2006; 108(4): 1374 - 1376. [Abstract] [Full Text] [PDF] E. H. Stover, J. Chen, C. Folens, B. H. Lee, N. Mentens, P. Marynen, I. R. Williams, D. G. Gilliland, and J. Cools Activation of FIP1L1-PDGFR{alpha} requires disruption of the juxtamembrane domain of PDGFR{alpha} and is FIP1L1-independent PNAS, May 23, 2006; 103(21): 8078 - 8083. [Abstract] [Full Text] [PDF] Y. Yamada, M. E. Rothenberg, A. W. Lee, H. S. Akei, E. B. Brandt, D. A. Williams, and J. A. Cancelas The FIP1L1-PDGFRA fusion gene cooperates with IL-5 to induce murine hypereosinophilic syndrome (HES)/chronic eosinophilic leukemia (CEL)-like disease Blood, May 15, 2006; 107(10): 4071 - 4079. [Abstract] [Full Text] [PDF] A. Tefferi, M. A. Elliott, and A. Pardanani Atypical Myeloproliferative Disorders: Diagnosis and Management Mayo Clin. Proc., April 1, 2006; 81(4): 553 - 563. [Abstract] [Full Text] [PDF] M. Serena, C. Guido, B. Emanuela, G. Enrico, S. Simona, C. Daniela, and M. 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[Abstract] [Full Text] [PDF] J. Apperley and B. Bain The FIP1L1-PDGFRA syndrome: a case of mistaken identity? Blood, November 15, 2004; 104(10): 2999 - 3000. [Full Text] [PDF] A. Pardanani, S. R. Brockman, S. F. Paternoster, H. C. Flynn, R. P. Ketterling, T. L. Lasho, C.-L. Ho, C.-Y. Li, G. W. Dewald, and A. Tefferi FIP1L1-PDGFRA fusion: prevalence and clinicopathologic correlates in 89 consecutive patients with moderate to severe eosinophilia Blood, November 15, 2004; 104(10): 3038 - 3045. [Abstract] [Full Text] [PDF] A. Pardanani and A. Tefferi Imatinib targets other than bcr/abl and their clinical relevance in myeloid disorders Blood, October 1, 2004; 104(7): 1931 - 1939. [Abstract] [Full Text] [PDF] A. D. Klion, M. A. Law, W. Riemenschneider, M. L. McMaster, M. R. Brown, M. Horne, B. Karp, M. Robinson, V. Sachdev, E. Tucker, et al. Familial eosinophilia: a benign disorder? Blood, June 1, 2004; 103(11): 4050 - 4055. [Abstract] [Full Text] [PDF] K. J. Smith, E. Jacobson, S. Hamza, and H. Skelton Unexplained Hypereosinophilia and the Need for Cytogenetic and Molecular Genetic Analyses Arch Dermatol, May 1, 2004; 140(5): 584 - 588. [Abstract] [Full Text] [PDF] J. Gotlib, J. Cools, J. M. Malone III, S. L. Schrier, D. G. Gilliland, and S. E. Coutre The FIP1L1-PDGFR{alpha} fusion tyrosine kinase in hypereosinophilic syndrome and chronic eosinophilic leukemia: implications for diagnosis, classification, and management Blood, April 15, 2004; 103(8): 2879 - 2891. [Abstract] [Full Text] [PDF] J. Cools, H. Quentmeier, B. J. P. Huntly, P. Marynen, J. D. Griffin, H. G. Drexler, and D. G. Gilliland The EOL-1 cell line as an in vitro model for the study of FIP1L1-PDGFRA-positive chronic eosinophilic leukemia Blood, April 1, 2004; 103(7): 2802 - 2805. [Abstract] [Full Text] [PDF] A. Pardanani, R. P. Ketterling, S. R. Brockman, H. C. Flynn, S. F. Paternoster, B. M. Shearer, T. L. Reeder, C.-Y. Li, N. C. P. Cross, J. Cools, et al. CHIC2 deletion, a surrogate for FIP1L1-PDGFRA fusion, occurs in systemic mastocytosis associated with eosinophilia and predicts response to imatinib mesylate therapy Blood, November 1, 2003; 102(9): 3093 - 3096. [Abstract] [Full Text] [PDF] A. Tefferi, A. Pardanani, C.-Y. Li, A. D. Klion, C. Akin, and T. B. Nutman Hypereosinophilic syndrome with elevated serum tryptase versus systemic mast cell disease associated with eosinophilia: 2 distinct entities? Blood, October 15, 2003; 102(8): 3073 - 3074. [Full Text] [PDF] Recent Articles on HES J Natl Cancer Inst, August 6, 2003; 95(15): 1103 - 1103. [Full Text]

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