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Blood, 15 May 2006, Vol. 107, No. 10, pp. 4071-4079. Prepublished online as a Blood First Edition Paper on January 17, 2006; DOI 10.1182/blood-2005-08-3153. This Article Full Text (PDF) All Versions of this Article: 2005-08-3153v1 107/10/4071    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 YAMADA, Y. Articles by CANCELAS, J. A Search for Related Content PubMed PubMed Citation Articles by YAMADA, Y. Articles by CANCELAS, J. A Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted August 5, 2005 Accepted January 7, 2006 The FIP1L1-PDGFR fusion gene cooperates with IL-5 to induce murine hypereosinophilic syndrome (HES)/chronic eosinophilic leukemia (CEL)-like disease YOSHIYUKI YAMADA, MARC E ROTHENBERG, ANDREW W LEE, HIROKO SAITO AKEI, ERIC B BRANDT, DAVID A WILLIAMS, and JOSE A CANCELAS* Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA Division of Experimental Hematology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA Division of Experimental Hematology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; Hoxworth Blood Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA * Corresponding author; email: jose.cancelas{at}chmcc.org. Dysregulated tyrosine kinase activity by the Fip-1-like 1 (FIP1L1)-platelet derived growth factor receptor alpha (PDGFR) (F/P) fusion gene has been identified as a cause of clonal hypereosinophilic syndrome (HES), called F/P-positive chronic eosinophilic leukemia (CEL) in human. However, transplantation of F/P-transduced hematopoietic stem cells/progenitors (F/P+ HSC/P) into mice results in chronic myelogenous leukemia-like disease, which does not resemble HES. Because a subgroup of patients with HES show T-cell dependent interleukin-5 (IL-5) overexpression, we determined if expression of the F/P fusion gene in the presence of transgenic T-cell IL-5 overexpression in mice induces HES-like disease. Mice transplanted with CD2-IL-5 transgenic F/P+ HSC/P (IL-5Tg-F/P) developed intense leukocytosis, strikingly high eosinophilia and eosinophilic infiltration of non-hematopoietic as well as hematopoietic tissues, a phenotype resembling human HES. The disease phenotype was transferable to secondary recipients transplanted at a high cell dose, suggesting involvement of a short-term repopulating stem cell or an early myeloid progenitor. Induction of significant eosinophilia was specific for F/P since expression of another fusion oncogene, p210-BCR/ABL in the presence of IL-5 overexpression was characterized by a significantly lower eosinophilia than IL-5Tg-F/P recipients. These results suggest that F/P is not sufficient to induce a HES/CEL-like disease but requires a second event associated with IL-5 overexpression. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: L. C. Kottyan, A. R. Collier, K. H. Cao, K. A. Niese, M. Hedgebeth, C. G. Radu, O. N. Witte, G. K. Khurana Hershey, M. E. Rothenberg, and N. Zimmermann Eosinophil viability is increased by acidic pH in a cAMP- and GPR65-dependent manner Blood, September 24, 2009; 114(13): 2774 - 2782. [Abstract] [Full Text] [PDF] K. Fukushima, I. Matsumura, S. Ezoe, M. Tokunaga, M. Yasumi, Y. Satoh, H. Shibayama, H. Tanaka, A. Iwama, and Y. Kanakura FIP1L1-PDGFR{alpha} Imposes Eosinophil Lineage Commitment on Hematopoietic Stem/Progenitor Cells J. Biol. Chem., March 20, 2009; 284(12): 7719 - 7732. [Abstract] [Full Text] [PDF] J. Cools FIP1L1/PDGFR{alpha}'s Kit to stimulate mast cells Blood, September 15, 2008; 112(6): 2179 - 2179. [Full Text] [PDF] Y. Yamada, A. Sanchez-Aguilera, E. B. Brandt, M. McBride, N. J. H. Al-Moamen, F. D. Finkelman, D. A. Williams, J. A. Cancelas, and M. E. Rothenberg FIP1L1/PDGFR{alpha} synergizes with SCF to induce systemic mastocytosis in a murine model of chronic eosinophilic leukemia/hypereosinophilic syndrome Blood, September 15, 2008; 112(6): 2500 - 2507. [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]

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