Genome-wide miRNA profiling in myelodysplastic syndrome with del(5q) treated with lenalidomide
Language English Country Great Britain, England Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
25287904
DOI
10.1111/ejh.12458
Knihovny.cz E-resources
- Keywords
- del(5q), lenalidomide, miRNA, myelodysplastic syndromes,
- MeSH
- Genome-Wide Association Study MeSH
- Chromosome Deletion MeSH
- Genetic Loci MeSH
- Haploinsufficiency MeSH
- Immunologic Factors therapeutic use MeSH
- Lenalidomide MeSH
- Leukocytes, Mononuclear drug effects metabolism pathology MeSH
- Middle Aged MeSH
- Humans MeSH
- Chromosomes, Human, Pair 14 MeSH
- Chromosomes, Human, Pair 5 genetics metabolism MeSH
- Anemia, Macrocytic drug therapy genetics metabolism pathology MeSH
- MicroRNAs genetics metabolism MeSH
- Myelodysplastic Syndromes drug therapy genetics metabolism pathology MeSH
- Primary Cell Culture MeSH
- Gene Expression Regulation, Neoplastic * MeSH
- Aged MeSH
- RNA Splicing MeSH
- Signal Transduction MeSH
- Gene Expression Profiling MeSH
- Case-Control Studies MeSH
- Thalidomide analogs & derivatives therapeutic use MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Immunologic Factors MeSH
- Lenalidomide MeSH
- MicroRNAs MeSH
- MIRN196 microRNA, human MeSH Browser
- MIRN34 microRNA, human MeSH Browser
- MIRN378 microRNA, human MeSH Browser
- MIRN451 microRNA, human MeSH Browser
- Thalidomide MeSH
OBJECTIVES: Lenalidomide is a potent drug with pleiotropic effects in patients with myelodysplastic syndrome (MDS) with deletion of the long arm of chromosome 5 [del(5q)]. We investigated its effect on regulation of microRNA (miRNA) expression profiles in del(5q) patients with MDS in vivo. METHODS: We used miRNA expression microarrays to study changes in miRNA levels in peripheral blood CD14+ monocytes collected from patients before and during lenalidomide treatment and compared them with those from healthy donors. RESULTS: Before treatment, we observed strong upregulation of pro-apoptotic miR-34a and miR-34a* that diminished during lenalidomide exposure. Upregulation of HOX-related miR-196b and erythroid-specific miR-451 seen in untreated patients remained unchanged after the treatment. At the time of hematologic response, expression of several miRNAs clustering to the 14q32 locus was reduced. Additionally, we focused more deeply on miRNAs from the 5q commonly deleted region and found that levels of miR-378 and miR-378* followed haploinsufficiency trend. CONCLUSIONS: This report describes changes in miRNA expression in del(5q) patients with MDS treated with lenalidomide, likely arising from deregulation of pathways implicated in lenalidomide action.
1st Department of Medicine General University Hospital Prague Czech Republic
Institute of Hematology and Blood Transfusion Prague Czech Republic
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