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DNA of Erythroid Origin Is Present in Human Plasma and Informs the Types of Anemia
- Source :
- Clinical Chemistry. 63:1614-1623
- Publication Year :
- 2017
- Publisher :
- Oxford University Press (OUP), 2017.
-
Abstract
- BACKGROUND There is much interest in the tissue of origin of circulating DNA in plasma. Data generated using DNA methylation markers have suggested that hematopoietic cells of white cell lineages are important contributors to the circulating DNA pool. However, it is not known whether cells of the erythroid lineage would also release DNA into the plasma. METHODS Using high-resolution methylation profiles of erythroblasts and other tissue types, 3 genomic loci were found to be hypomethylated in erythroblasts but hypermethylated in other cell types. We developed digital PCR assays for measuring erythroid DNA using the differentially methylated region for each locus. RESULTS Based on the methylation marker in the ferrochelatase gene, erythroid DNA represented a median of 30.1% of the plasma DNA of healthy subjects. In subjects with anemia of different etiologies, quantitative analysis of circulating erythroid DNA could reflect the erythropoietic activity in the bone marrow. For patients with reduced erythropoietic activity, as exemplified by aplastic anemia, the percentage of circulating erythroid DNA was decreased. For patients with increased but ineffective erythropoiesis, as exemplified by β-thalassemia major, the percentage was increased. In addition, the plasma concentration of erythroid DNA was found to correlate with treatment response in aplastic anemia and iron deficiency anemia. Plasma DNA analysis using digital PCR assays targeting the other 2 differentially methylated regions showed similar findings. CONCLUSIONS Erythroid DNA is a hitherto unrecognized major component of the circulating DNA pool and is a noninvasive biomarker for differential diagnosis and monitoring of anemia.
- Subjects :
- 0301 basic medicine
Ineffective erythropoiesis
Erythroblasts
Clinical Biochemistry
Biology
medicine.disease_cause
Diagnosis, Differential
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
hemic and lymphatic diseases
medicine
Humans
Erythropoiesis
Aplastic anemia
Gene
Anemia, Iron-Deficiency
beta-Thalassemia
Biochemistry (medical)
Anemia, Aplastic
Anemia
DNA
Methylation
DNA Methylation
medicine.disease
Molecular biology
030104 developmental biology
Differentially methylated regions
medicine.anatomical_structure
chemistry
Myelodysplastic Syndromes
030220 oncology & carcinogenesis
DNA methylation
Bone marrow
Ferrochelatase
Subjects
Details
- ISSN :
- 15308561 and 00099147
- Volume :
- 63
- Database :
- OpenAIRE
- Journal :
- Clinical Chemistry
- Accession number :
- edsair.doi.dedup.....c834796ccfb065074c095fd07216845d