Up-regulation of ribosomal genes is associated with a poor response to azacitidine in myelodysplasia and related neoplasms
Jazyk angličtina Země Japonsko Médium print-electronic
Typ dokumentu časopisecké články
PubMed
27416819
DOI
10.1007/s12185-016-2058-3
PII: 10.1007/s12185-016-2058-3
Knihovny.cz E-zdroje
- Klíčová slova
- Azacitidine, Gene expression profiling, Myelodysplastic syndromes, Ribosomal genes,
- MeSH
- akutní myeloidní leukemie genetika MeSH
- azacytidin farmakologie terapeutické užití MeSH
- buňky kostní dřeně metabolismus MeSH
- chronická myelomonocytární leukemie genetika MeSH
- lidé MeSH
- myelodysplastické syndromy farmakoterapie genetika MeSH
- proliferace buněk genetika MeSH
- ribozomální proteiny genetika MeSH
- terapie neúspěšná MeSH
- transkriptom účinky léků MeSH
- upregulace účinky léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- azacytidin MeSH
- ribozomální proteiny MeSH
Azacitidine (AZA) is a hypomethylating drug used to treat disorders associated with myelodysplasia and related neoplasms. Approximately 50 % of patients do not respond to AZA and have very poor outcomes. There is thus great interest in identifying predictive biomarkers for AZA responsiveness. We searched for specific genes whose expression level was associated with response status. Using microarrays, we analyzed gene expression patterns in bone marrow CD34+ cells in serial samples from 32 patients with myelodysplastic syndromes, chronic myelomonocytic leukemia, and acute myeloid leukemia with myelodysplasia-related changes before and during the AZA therapy. At baseline, a comparison of the responders and non-responders showed 52 differentially expressed genes (P < 0.01). Functional annotation of the deregulated genes revealed categories primarily related to ribosomes and pathways associated with proliferation. The expression level of RPL28 correlated with overall survival. We identified altered expression in 167 genes in responders, 26 genes in non-responders with stable disease, and 13 genes in non-responders with disease progression using paired t test of expression levels in patients before and during treatment. Our data indicate that AZA treatment failure is associated with the up-regulation of ribosomal genes/pathways that are likely related to intensive proteosynthesis in proliferative/neoplastic cells of non-responders.
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