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Blood, 15 February 2007, Vol. 109, No. 4, pp. 1687-1691. Prepublished online as a Blood First Edition Paper on November 7, 2006; DOI 10.1182/blood-2006-05-025395. This Article Full Text Full Text (PDF) Supplemental Figure All Versions of this Article: blood-2006-05-025395v1 109/4/1687    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 HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Kim, A. Articles by Largaespada, D. A. Search for Related Content PubMed PubMed Citation Articles by Kim, A. Articles by Largaespada, D. A. Related Collections Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA ß common receptor inactivation attenuates myeloproliferative disease in Nf1 mutant mice Andrew Kim1, Kelly Morgan2, Diane E. Hasz2, Stephen M. Wiesner2, Jennifer O. Lauchle1, Jennifer L. Geurts2, Miechaleen D. Diers2, Doan T. Le1, Scott C. Kogan3,4, Luis F. Parada5, Kevin Shannon1,4, and David A. Largaespada2 1 Department of Pediatrics, University of California San Francisco; 2 Department of Genetics, Cell Biology and Development, and Cancer Center, University of Minnesota, Minneapolis; 3 Department of Laboratory Medicine and 4 Cancer Center, University of California San Francisco; 5 Center for Developmental Biology and Kent Waldrep Foundation Center for Basic Neuroscience Research on Nerve Growth and Regeneration, University of Texas Southwestern Medical Center, Dallas Neurofibromatosis type 1 (NF1) syndrome is caused by germline mutations in the NF1 tumor suppressor, which encodes neurofibromin, a GTPase activating protein for Ras. Children with NF1 are predisposed to juvenile myelomonocytic leukemia (JMML) and lethally irradiated mice given transplants with homozygous Nf1 mutant (Nf1–/–) hematopoietic stem cells develop a fatal myeloproliferative disorder (MPD) that models JMML. We investigated the requirement for signaling through the GM-CSF receptor to initiate and sustain this MPD by generating Nf1 mutant hematopoietic cells lacking the common ß chain (Beta c) of the GM-CSF receptor. Mice reconstituted with Nf1–/–, beta c–/– stem cells did not develop evidence of MPD despite the presence of increased number of immature hematopoietic progenitors in the bone marrow. Interestingly, when the Mx1-Cre transgene was used to inactivate a conditional Nf1 mutant allele in hematopoietic cells, concomitant loss of beta c–/–reduced the severity of the MPD, but did not abrogate it. Whereas inhibiting GM-CSF signaling may be of therapeutic benefit in JMML, our data also demonstrate aberrant proliferation of Nf1–/–myeloid progenitors that is independent of signaling through the GM-CSF receptor. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: D. L. Waning, B. Li, N. Jia, Y. Naaldijk, W. S. Goebel, H. HogenEsch, and K. T. Chun Cul4A is required for hematopoietic cell viability and its deficiency leads to apoptosis Blood, July 15, 2008; 112(2): 320 - 329. [Abstract] [Full Text] [PDF]

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