Epigenetics of multiple myeloma after treatment with cytostatics and gamma radiation
Language English Country England, Great Britain Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
19362368
DOI
10.1016/j.leukres.2009.03.016
PII: S0145-2126(09)00139-8
Knihovny.cz E-resources
- MeSH
- Apoptosis MeSH
- Chromatin Immunoprecipitation MeSH
- Cyclin D1 genetics MeSH
- DNA Primers MeSH
- Epigenesis, Genetic * MeSH
- Genes, myc MeSH
- Combined Modality Therapy MeSH
- Humans MeSH
- Multiple Myeloma drug therapy genetics pathology radiotherapy MeSH
- Polymerase Chain Reaction MeSH
- Cell Proliferation MeSH
- Antineoplastic Agents therapeutic use MeSH
- Flow Cytometry MeSH
- Base Sequence MeSH
- Gamma Rays therapeutic use MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- CCND1 protein, human MeSH Browser
- Cyclin D1 MeSH
- DNA Primers MeSH
- Antineoplastic Agents MeSH
Genetic and epigenetic changes in multiple myeloma (MM) correlate with the stage of the disease. Therefore, we investigated how cytostatics and gamma radiation influence MM-associated histone modifications. ChIP-PCR and ChIP-on-chip technologies were used to quantify H3K9 acetylation and H3K9 dimethylation at select loci in MM patients, lymphoblastoid ARH-77, and myeloma MOLP-8 cells. Genome-wide analysis revealed that the cytostatic, melphalan, increased H3K9 acetylation at multiple gene promoters in ARH-77 cells. Melphalan and gamma radiation also influenced histone modification of prognostically important c-myc and CCND1 genes in ARH-77 and MOLP-8 cells. Moreover, H3K9 acetylation at c-myc and CCND1 promoters was increased in individual MM patients after melphalan treatment. Western blotting revealed that these effects were accompanied by changes in c-MYC and cyclin D1 protein levels. Taken together, we showed that cytostatics significantly alter histone modification of tumor-related genes which is indispensable for understanding cancer therapies.
References provided by Crossref.org
Structure and epigenetics of nucleoli in comparison with non-nucleolar compartments