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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 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 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 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 Neoplasia Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA FIP1L1/PDGFR synergizes with SCF to induce systemic mastocytosis in a murine model of chronic eosinophilic leukemia/hypereosinophilic syndrome Yoshiyuki Yamada1, Abel Sanchez-Aguilera2, Eric B. Brandt1, Melissa McBride1, Nabeel J. H. Al-Moamen3, Fred D. Finkelman4, David A. Williams5, Jose A. Cancelas2,6,*, and Marc E. Rothenberg1,* 1 Division of Allergy and Immunology, and 2 Division of Experimental Hematology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, OH; 3 Department of Molecular Genetics, Biochemistry, and Microbiology, and 4 Division of Immunology, Department of Internal Medicine, University of Cincinnati College of Medicine, OH; 5 Division of Hematology/Oncology, Boston Children's Hospital, Harvard Medical School, MA; and 6 Hoxworth Blood Center, University of Cincinnati College of Medicine, OH 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 (HSCs/Ps) 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 that received a transplant of IL-5 transgenic HSCs/Ps. 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 HSCs/Ps showed proliferation and MC differentiation in vitro in the absence of cytokines. SCF stimulated greater migration of F/P-expressing MCs than mock vector–transduced MCs. F/P-expressing bone marrow–derived mast cells (BMMCs) survived longer than mock vector control BMMCs 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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