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Blood, 15 September 2008, Vol. 112, No. 6, pp. 2500-2507. Prepublished online as a Blood First Edition Paper on June 6, 2008; DOI 10.1182/blood-2007-11-126268. This Article Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2007-11-126268v1 112/6/2500    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 CrossRef Citing Articles via Google Scholar Google Scholar Articles by Yamada, Y. Articles by Rothenberg, M. E Search for Related Content PubMed PubMed Citation Articles by Yamada, Y. Articles by Rothenberg, M. E Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted November 29, 2007 Accepted April 20, 2008 FIP1L1/PDGFR synergizes with SCF to induce systemic mastocytosis in a murine model of chronic eosinophilic leukemia/hypereosinophilic syndrome Yoshiyuki Yamada, Abel Sanchez-Aguilera, Eric B Brandt, Melissa McBride, Nabeel JH Al-Moamen, Fred D Finkelman, David A Williams, Jose A Cancelas, and Marc E Rothenberg* Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States Division of Experimental Hematology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati College of Medicine, Cincinnati, Ohio, United States Division of Immunology, University of Cincinnati College of Medicine, Cincinnati, Ohio, United States Division of Hematology/Oncology, Children's Hospital, Harvard Medical School, Boston, MA, United States Hoxworth Blood Center, University of Cincinnati College of Medicine, Cincinnati, OH, United States * Corresponding author; email: rothenberg{at}cchmc.org. Expression of the fusion gene FIP1-like 1/platelet-derived growth factor receptor alpha (FIP1L1/PDGFR, F/P) and dysregulated c-kit tyrosine kinase activity are associated with systemic mastocytosis (SM) and chronic eosinophilic leukemia (CEL) /hypereosinophilic syndrome (HES). We analyzed SM development and pathogenesis in a murine CEL model induced by F/P in hematopoietic stem cells and progenitors (HSC/P) and T-cell overexpression of IL-5 (F/P positive CEL mice). These mice had more mast cell (MC) infiltration in the bone marrow (BM), spleen, skin and small intestine than control mice transplanted with IL-5 transgenic HSC/P. Moreover, intestinal MC infiltration induced by F/P expression was severely diminished, but not abolished, in mice injected with neutralizing anti-c-kit antibody, suggesting that endogenous stem cell factor (SCF)/c-kit interaction synergizes with F/P expression to induce SM. F/P-expressing BM HSC/P showed proliferation and MC differentiation in vitro in the absence of cytokines. SCF stimulated significantly greater migration of F/P-expressing MC than mock vector-transduced MC. F/P-expressing BMMC survived longer than mock-vector control BMMC in cytokine-deprived conditions. The increased proliferation and survival correlated with increased SCF-induced Akt activation. In summary, F/P synergistically promotes MC development, activation and survival in vivo and in vitro in response to SCF. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: FIP1L1/PDGFR's Kit to stimulate mast cells Jan Cools Blood 2008 112: 2179. [Full Text] [PDF]

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