DNA instability in low-risk myelodysplastic syndromes: refractory anemia with or without ring sideroblasts
| Autor: | Bozena Novotna, Radana Neuwirtova, Yana Bagryantseva, Magda Siskova |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Adult
Male Genome instability Myeloid DNA damage Biology Genomic Instability hemic and lymphatic diseases Genetics medicine Humans Molecular Biology Genetics (clinical) Aged Aged 80 and over Cytopenia Myelodysplastic syndromes Anemia Refractory DNA General Medicine Middle Aged Hematopoietic Stem Cells medicine.disease Comet assay Haematopoiesis medicine.anatomical_structure Immunology Cancer research Female Comet Assay Bone marrow DNA Damage |
| Zdroj: | Human Molecular Genetics. 17:2144-2149 |
| ISSN: | 1460-2083 0964-6906 |
| DOI: | 10.1093/hmg/ddn113 |
| Popis: | We tested genomic instability in patients with myelodysplastic syndrome (MDS) by the comet assay and verified the suitability of this approach as a tool for analysis of ineffective hematopoiesis in refractory anemia (RA) and RA with ring sideroblasts (RARS). Erythroid and myeloid cell populations from bone marrow aspirates of 20 RA, 14 RARS and 15 control subjects were separated by differential expression of glycophorin A and subjected to comet assay. The extent of DNA migration was measured in single cells (200 cells/bone marrow fraction/subject). The results were in agreement with the concept of increased apoptosis in low-risk MDS subtypes. The RA samples had a significantly higher DNA instability than controls in glycophorin A positive cells, and the extent of DNA breakage correlated with the degree of cytopenia. Although RARS had an even higher rate of genomic instability in bone marrow cells than RA, there was no clear relationship to peripheral cytopenia. This suggests an additional DNA instability of non-apoptotic origin. Whether this increase is associated with an increased repair of oxidative damage in DNA arising due to iron deposits in ring sideroblasts remains to be formally proven. Comet assay provides a promising tool for the investigation of difference between RA and RARS pathobiology. |
| Databáze: | OpenAIRE |
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