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Blood, 1 May 2005, Vol. 105, No. 9, pp. 3731-3736. Prepublished online as a Blood First Edition Paper on January 11, 2005; DOI 10.1182/blood-2004-06-2094. This Article Full Text (PDF) All Versions of this Article: 2004-06-2094v1 105/9/3731    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 Wolfler, A. Articles by Sill, H. Search for Related Content PubMed PubMed Citation Articles by Wolfler, A. Articles by Sill, H. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted June 7, 2004 Accepted January 6, 2005 A functional single nucleotide polymorphism of the G-CSF receptor gene predisposes to high-risk myelodysplastic syndrome Albert Wolfler, Stefan J Erkeland, Claudia Bodner, Marijke Valkhof, Wilfried Renner, Christina Leitner, Werner Olipitz, Michael Pfeilstocker, Christoph Tinchon, Werner Emberger, Werner Linkesch, Ivo P Touw, and Heinz Sill* Division of Hematology, Medical University, Graz, Austria Department of Hematology, Erasmus University Medical Center, Rotterdam, The Netherlands Clinical Institute for Medical and Chemical Laboratory Diagnostics, Medical University, Graz, Austria Third Medical Department and Ludwig Boltzmann Institute for Leukemia Research and Hematology, Hanusch Hospital, Vienna, Austria Division of Hematology and Oncology, General Hospital Leoben, Leoben, Austria Institute of Medical Biology and Human Genetics, Medical University, Graz, Austria * Corresponding author; email: heinz.sill{at}meduni-graz.at. The granulocyte colony-stimulating factor receptor (G-CSF-R) transmits signals for proliferation and differentiation of myeloid progenitor cells. Here we report on the identification of a rare single nucleotide polymorphism within its intracellular domain (G-CSF-R_Glu785Lys). Screening a cohort of 116 patients with primary myelodysplastic syndromes (MDS), de novo AML (84 patients) as well as 232 age- and sex-matched controls revealed a highly significant association of the G-CSF-R_785Lys allele with the development of high-risk MDS as defined by >5% bone marrow blasts (9.7% vs. 0.9% in controls; p=0.001; odds ratio (OR) 12.5, 95% CI 2.4-58.9) or an international prognostic score of intermediate-2 or high (13.0% vs. 0.9%; p<0.001; OR 14.0, 95% CI 3.4-85.0). Functional analysis by retroviral transfer of G-CSF-R_785Lys into myeloid progenitor cells of G-CSF-R deficient mice showed a significantly diminished colony formation capacity after G-CSF stimulation as compared to cells transduced with the wildtype receptor. These results suggest that lifelong altered G-CSF response by the G-CSF-R_785Lys may render individuals susceptible to development of high-risk MDS. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. H. Tomasson, Z. Xiang, R. Walgren, Y. Zhao, Y. Kasai, T. Miner, R. E. Ries, O. Lubman, D. H. Fremont, M. D. McLellan, et al. Somatic mutations and germline sequence variants in the expressed tyrosine kinase genes of patients with de novo acute myeloid leukemia Blood, May 1, 2008; 111(9): 4797 - 4808. [Abstract] [Full Text] [PDF]

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