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A functional single-nucleotide polymorphism of the G-CSF receptor gene predisposes individuals to high-risk myelodysplastic syndrome.

Authors: Wolfler, A  Erkeland, SJ  Bodner, C  Valkhof, M  Renner, W  Leitner, C  Olipitz, W  Pfeilstocker, M  Tinchon, C  Emberger, W  Linkesch, W  Touw, IP  Sill, H 
Citation: Wolfler A, etal., Blood. 2005 May 1;105(9):3731-6. Epub 2005 Jan 11.
Pubmed: (View Article at PubMed) PMID:15644419
DOI: Full-text: DOI:10.1182/blood-2004-06-2094

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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CRRD Object Information
CRRD ID: 10450471
Created: 2016-01-13
Species: All species
Last Modified: 2016-01-13
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.