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Blood, 7 May 2009, Vol. 113, No. 19, pp. 4690-4701. Prepublished online as a Blood First Edition Paper on February 19, 2009; DOI 10.1182/blood-2008-05-158485. This Article Full Text Full Text (PDF) Supplemental Table and Figures All Versions of this Article: blood-2008-05-158485v1 113/19/4690    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 Koenigsmann, J. Articles by Carstanjen, D. Search for Related Content PubMed PubMed Citation Articles by Koenigsmann, J. Articles by Carstanjen, D. Related Collections Myeloid Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  MYELOID NEOPLASIA Nf1 haploinsufficiency and Icsbp deficiency synergize in the development of leukemias Jessica Koenigsmann1, Cornelia Rudolph2, Sandrine Sander3, Olivia Kershaw4, Achim D. Gruber4, Lars Bullinger5, Brigitte Schlegelberger2, and Dirk Carstanjen1 1 Leibniz-Institut fuer Molekulare Pharmakologie, Berlin; 2 Institute of Cell and Molecular Pathology, Hannover Medical School, Hannover; 3 Department of Physiological Chemistry, University of Ulm, Ulm; 4 Department of Veterinary Pathology, Freie Universitaet Berlin, Berlin; and 5 Department of Internal Medicine III, University of Ulm, Ulm, Germany Loss of neurofibromin or interferon consensus sequence binding protein (Icsbp) leads to a myeloproliferative disorder. Transcription of NF1 is directly controlled by ICSBP. It has been postulated that loss of NF1 expression resulting from loss of transcriptional activation by ICSBP contributes to human hematologic malignancies. To investigate the functional cooperation of these 2 proteins, we have established Icsbp-deficient mice with Nf1 haploinsufficiency. We here demonstrate that loss of Icsbp and Nf1 haploinsufficiency synergize to induce a forced myeloproliferation in Icsbp-deficient mice because of an expansion of a mature myeloid progenitor cell. Furthermore, Nf1 haploinsufficiency and loss of Icsbp contribute synergistically to progression of the myeloproliferative disorder toward transplantable leukemias. Leukemias are characterized by distinct phenotypes, which correlate with progressive genetic abnormalities. Loss of Nf1 heterozygosity is not mandatory for disease progression, but its occurrence with other genetic abnormalities indicates progressive genetic alterations in a defined subset of leukemias. These data show that loss of the 2 tumor suppressor genes Nf1 and Icsbp synergize in the induction of leukemias. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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