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Blood, 1 March 2007, Vol. 109, No. 5, pp. 2139-2146. Prepublished online as a Blood First Edition Paper on October 19, 2006; DOI 10.1182/blood-2005-11-026823. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2005-11-026823v1 109/5/2139    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 Cervi, D. Articles by Ben-David, Y. Search for Related Content PubMed PubMed Citation Articles by Cervi, D. Articles by Ben-David, Y. Related Collections Oncogenes and Tumor Suppressors Hemostasis, Thrombosis, and Vascular Biology Immunobiology Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Enhanced natural-killer cell and erythropoietic activities in VEGF-A–overexpressing mice delay F-MuLV–induced erythroleukemia David Cervi1, Yuval Shaked1, Mehran Haeri1, Tatiana Usenko1, Christina R. Lee1, Jody J. Haigh2, Andras Nagy3, Robert S. Kerbel1, Eitan Yefenof4, and Yaacov Ben-David1 1 Department of Molecular and Cellular Biology, Sunnybrook Health Sciences Centre, Toronto, ON, Canada; 2 Department for Molecular Biomedical Research, Flanders Interuniversity Institute for Biotechnology (VIB), Ghent University, Zwijnaarde, Belgium; 3 Department of Molecular and Medical Genetics, University of Toronto, and Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON, Canada; 4 Lautenberg Center of Immunology, Hadassah Medical School, Jerusalem, Israel We have previously reported that VEGF-A, in combination with MCP-5, contributes to leukemia progression within the splenic microenvironment of mice infected with F-MuLV. To study the influence of constitutively elevated VEGF-A levels on the progression of erythroleukemia, mice heterozygous for a VEGF-A "hypermorphic" allele (Vegfhi/+) were inoculated with F-MuLV. Unexpectedly, a significant delay in erythroleukemia was observed in Vegfhi/+ mice when compared with wild-type controls. These results suggested an altered physiologic response arising from elevated VEGF-A levels that decelerated erythroleukemic progression. Characterization of hematopoiesis in Vegfhi/+ spleens showed a higher natural killer cell activity, elevated B cells, and a decrease in T-cell number. Furthermore, higher erythroid progenitors (ie, CD34+, CD36+, and Ter119+ cells) were evident in the bone marrow, spleen, and peripheral blood of Vegfhi/+ mice. The CFU-E levels were significantly elevated in Vegfhi/+ bone marrow cultures, and this elevation was blocked by a neutralizing antibody to VEGF-A receptor (VEGFR-2). Moreover, erythroleukemic mice were treated with recombinant erythropoietin and, similar to diseased Vegfhi/+ mice, showed a delay in disease progression. We propose that a compensatory erythropoietic response combined with increased natural killer (NK) cell activity account for the extended survival of erythroleukemic, Vegfhi/+ mice. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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