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Prepublished online as a Blood First Edition Paper on October 17, 2002; DOI 10.1182/blood-2002-08-2635. This Article Full Text (PDF) All Versions of this Article: 2002-08-2635v1 101/5/1984    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 Ingram, D. A Articles by Clapp, D W Search for Related Content PubMed PubMed Citation Articles by Ingram, D. A Articles by Clapp, D W Social Bookmarking                   What's this? Submitted August 28, 2002 Accepted October 4, 2002 Leukemic potential of doubly mutant Nf1 and Wv hematopoietic cells David A Ingram*, Mary Jo Wenning, Kevin Shannon, and D W Clapp Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, USA Department of Pediatrics, University of California at San Francisco, San Francisco, CA, USA Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, USA; Department of Microbiology/Immunology, Indiana University School of Medicine, Indianapolis, IN, USA * Corresponding author; email: dingram{at}iupui.edu. The development of molecularly targeted treatments of adult leukemias warrants investigation of these targets in similar pediatric leukemias. The NF1 tumor suppressor gene, which encodes a GTPase activating protein (GAP) for p21ras, is frequently inactivated in juvenile myelomonocytic leukemia (JMML). Other patients with JMML acquire activating RAS gene mutations. Recipient mice reconstituted with Nf1 -/- fetal hematopoietic cells develop a myeloproliferative disease (MPD) that models the human disease. JMML arises from clonal expansion of a hematopoietic stem cell (HSC), and JMML cells and murine Nf1-/- hematopoietic cells are hypersensitive to granulocyte macrophage-colony stimulating factor (GM-CSF) and KitL, the ligand for c-kit. We generated embryos doubly mutant for the Wv allele of c-kit and Nf1 to ask if reduction of c-kit activity would delay or prevent the development of MPD. Despite a reduction in c-kit activity to approximately 10% of wildtype levels, Nf1 -/-;Wv/Wv cells induced MPD in recipient mice. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: L. S. Haneline, H. White, F.-C. Yang, S. Chen, C. Orschell, R. Kapur, and D. A. Ingram Genetic reduction of class IA PI-3 kinase activity alters fetal hematopoiesis and competitive repopulating ability of hematopoietic stem cells in vivo Blood, February 15, 2006; 107(4): 1375 - 1382. [Abstract] [Full Text] [PDF] T. Illmer, C. Thiede, A. Fredersdorf, S. Stadler, A. Neubauer, G. Ehninger, and M. Schaich Activation of the RAS Pathway Is Predictive for a Chemosensitive Phenotype of Acute Myelogenous Leukemia Blasts Clin. Cancer Res., May 1, 2005; 11(9): 3217 - 3224. [Abstract] [Full Text] [PDF] C. Zhu, G. Saberwal, Y. Lu, L. C. Platanias, and E. A. Eklund The Interferon Consensus Sequence-binding Protein Activates Transcription of the Gene Encoding Neurofibromin 1 J. Biol. Chem., December 3, 2004; 279(49): 50874 - 50885. [Abstract] [Full Text] [PDF] K. Hiatt, D. A. Ingram, H. Huddleston, D. F. Spandau, R. Kapur, and D. W. Clapp Loss of the Nf1 Tumor Suppressor Gene Decreases Fas Antigen Expression in Myeloid Cells Am. J. Pathol., April 1, 2004; 164(4): 1471 - 1479. [Abstract] [Full Text] [PDF]

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