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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 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 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 Wölfler, A. Articles by Sill, H. Search for Related Content PubMed PubMed Citation Articles by Wölfler, A. Articles by Sill, H. Related Collections Hematopoiesis and Stem Cells Neoplasia Signal Transduction Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA A functional single-nucleotide polymorphism of the G-CSF receptor gene predisposes individuals to high-risk myelodysplastic syndrome Albert Wölfler, Stefan J. Erkeland, Claudia Bodner, Marijke Valkhof, Wilfried Renner, Christina Leitner, Werner Olipitz, Michael Pfeilstöcker, Christoph Tinchon, Werner Emberger, Werner Linkesch, Ivo P. Touw, and Heinz Sill From the 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, Austria; and Institute of Medical Biology and Human Genetics, Medical University Graz, Austria. 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 acute myeloid leukemia (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 more than 5% bone marrow blasts (9.7% versus 0.9% in controls; P = .001; odds ratio [OR], 12.5; 95% confidence interval [CI], 2.4-58.9) or an International Prognostic Scoring System score of intermediate-2 or high (13.0% versus 0.9%; P < .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 with cells transduced with the wild-type 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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