Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Wölfler, A; Erkeland, SJ; Bodner, C; Valkhof, M; Renner, W; Leitner, C; Olipitz, W; Pfeilstöcker, M; Tinchon, C; Emberger, W; Linkesch, W; Touw, IP; Sill, H.
A functional single-nucleotide polymorphism of the G-CSF receptor gene predisposes individuals to high-risk myelodysplastic syndrome.
Blood. 2005; 105(9):3731-3736
Doi: 10.1182/blood-2004-06-2094
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- Führende Autor*innen der Med Uni Graz
- Sill Heinz
- Wölfler Albert
- Co-Autor*innen der Med Uni Graz
- Emberger Werner
- Leitner Christina
- Linkesch Werner
- Olipitz Werner
- Renner Wilfried
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- Abstract:
- 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.
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- Acute Disease -
- Adult -
- Aged -
- Aged, 80 and over -
- Animals -
- Case-Control Studies -
- Cells, Cultured -
- Female -
- Genetic Predisposition to Disease -
- Genetic Testing -
- Hematopoietic Stem Cells -
- Humans -
- Leukemia, Myeloid - genetics
- Male -
- Mice -
- Mice, Knockout -
- Middle Aged -
- Myelodysplastic Syndromes - etiology Myelodysplastic Syndromes - genetics Myelodysplastic Syndromes - pathology
- Myeloid Progenitor Cells - metabolism Myeloid Progenitor Cells - transplantation
- Polymorphism, Single Nucleotide -
- Receptors, Granulocyte Colony-Stimulating Factor - genetics
- Risk -
- Transduction, Genetic -
- Transfection -