Growth differentiation factor 15 production is necessary for normal erythroid differentiation and is increased in refractory anaemia with ring-sideroblasts
Open accessAbstract
The disturbed erythropoiesis in patients with refractory anaemia with ring-sideroblasts (RARS) is characterized by intramedullary apoptosis of erythroid precursors and increased iron accumulation in mitochondria. To gain insight into these pathophysiological mechanisms we compared the gene expression profile (GEP) of erythroid precursors from RARS patients to the GEP of normal erythroid precursors. Three hundred sixty four probe sets were up-, and 253 probe sets downregulated in RARS cells. Interestingly, Growth Differentiation factor 15 (GDF15), a cytokine from the TGFbeta family, was dramatically upregulated in all RARS patients. Measurement of GDF15 in the sera from twenty RARS patients confirmed this finding by showing significantly, 7.2-fold, increased protein levels (3254 +/- 1400 ng/ml vs. 451 +/- 87 ng/ml in normals). In vitro studies demonstrated erythroid-specific production of GDF15 and dependence on erythropoietin. Induction of apoptosis by arsenic trioxide, a drug which acts via reduction of the mitochondrial membrane potential, also stimulated GDF15 production. Downregulation of endogenous GDF15 production in erythoblasts by specific siRNA led to diminished erythroid differentiation. Taken together, our findings demonstrate a new role for GDF15 in normal erythropoiesis as well as in the ineffective erythropoiesis of RARS patients.
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Increased GDF15 serum levels associate with syndromes of ineffective erythropoiesis, for example α- and β-thalassemia.
“While increased GDF15 serum levels associate with syndromes of ineffective erythropoiesis, for example α- and β-thalassemia”
From Regulation of erythropoiesis by hypoxia-inducible factors (2013) · cites this paper as [219]
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- Authors
- Ramirez, J., Schaad, O., Durual, S., Cossali, D., Docquier, M., Beris, P., Descombes, P., & Matthes, T.
- Affiliations
- University Hospital of Geneva (CH)
- University of Geneva (CH)
- Corresponding author
- Matthes, Thomas
- Venue
- British Journal of Haematology
- Publisher
- Wiley
- Published
- 2008-12-17
- Volume
- 144
- Issue
- 2
- Pages
- 251-262
- ISSN
- 0007-1048 (ISSN-L)
- 1365-2141
- OpenAlex
- W1983658905
- Cited by
- 96
- References
- 37
- Citations by year
- 2025: 3 · 2024: 4 · 2023: 3 · 2022: 2 · 2021: 4 · 2020: 6 · 2019: 4 · 2018: 2 · 2017: 6 · 2016: 4 · 2015: 8 · 2014: 3 · 2013: 8 · 2012: 9
- FWCI
- 6.90
- Type
- journal article
- Language
- en
- Open access
- Locations
- British Journal of Haematology (publishedVersion)
- PubMed (publishedVersion)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
- HAL (submittedVersion)
- Topics
- Health Sciences › Medicine › Rheumatology › GDF15 and Related Biomarkers
- Health Sciences › Medicine › Hematology › Erythropoietin and Anemia Treatment
- Health Sciences › Medicine › Genetics › Hemoglobinopathies and Related Disorders
- Keywords
- growth differentiation factor 15, erythroid differentiation, erythropoiesis, erythroid precursors, gene expression profiling, erythropoietin, arsenic trioxide, apoptosis, mitochondrial iron accumulation, siRNA knockdown
- MeSH terms
- Aged, Aged, 80 and over, Anemia, Refractory, Anemia, Sideroblastic, Cell Differentiation, Cell Separation, Erythropoiesis, Humans, Middle Aged, Erythroid Precursor Cells, Case-Control Studies, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, Growth Differentiation Factor 15
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