Contributions
Abstract: PB1640
Type: Publication Only
Session title: Myeloma and other monoclonal gammopathies - Biology & Translational Research
Background
Epigenetic regulations play an important role in the etiopathogenesis of multifactorial diseases such as multiple myeloma. DNA methylation is the most studied epigenetic modification and has an impact on gene expression and genome stability.
Aims
The gene expression profile was compared with DNA methylation level in selected promoter regions of two tumor suppressor genes.
Methods
5 samples of bone marrow aspirates (after sorting of CD138+ cells) were used for quantification of RBP1 and GPX3 genes expressions followed by pyrosequencing methylation analysis of the promoter gene sequence. These expression and methylation analysis of studied tumor suppressor genes were also performed in myeloma cell lines KMS12-BM and KMS12-PE after their treatment with demethylation agents, 5-aza-2´-deoxycytidine and 5-azacytidine.
Results
In CD138+ sorted patient samples, strong negative correlation (r = -0,635) between GPX3 gene expression and its promoter gene sequence methylation was determined, and the low negative correlation was detected in two from three analysed promoter sequences of RBP1 gene (r = -0,304 for As11; r = -0,154 for As10; r = 0,207 for As12). In comparison to untreated cells, the re-expression and/or increased expression of RBP1 and GPX3 genes after their demethylation treatment of both KMS12-BM and KMS12-PE cell lines was found.
Conclusion
Negative correlation between gene expression and promoter gene methylation of both studied GPX3 and RBP1 genes indicates DNA methylation impact on expression of these tumor suppressors, which could play an important role in myelomagenesis.
Keyword(s): DNA methylation, Gene expression, Tumor suppressor
Abstract: PB1640
Type: Publication Only
Session title: Myeloma and other monoclonal gammopathies - Biology & Translational Research
Background
Epigenetic regulations play an important role in the etiopathogenesis of multifactorial diseases such as multiple myeloma. DNA methylation is the most studied epigenetic modification and has an impact on gene expression and genome stability.
Aims
The gene expression profile was compared with DNA methylation level in selected promoter regions of two tumor suppressor genes.
Methods
5 samples of bone marrow aspirates (after sorting of CD138+ cells) were used for quantification of RBP1 and GPX3 genes expressions followed by pyrosequencing methylation analysis of the promoter gene sequence. These expression and methylation analysis of studied tumor suppressor genes were also performed in myeloma cell lines KMS12-BM and KMS12-PE after their treatment with demethylation agents, 5-aza-2´-deoxycytidine and 5-azacytidine.
Results
In CD138+ sorted patient samples, strong negative correlation (r = -0,635) between GPX3 gene expression and its promoter gene sequence methylation was determined, and the low negative correlation was detected in two from three analysed promoter sequences of RBP1 gene (r = -0,304 for As11; r = -0,154 for As10; r = 0,207 for As12). In comparison to untreated cells, the re-expression and/or increased expression of RBP1 and GPX3 genes after their demethylation treatment of both KMS12-BM and KMS12-PE cell lines was found.
Conclusion
Negative correlation between gene expression and promoter gene methylation of both studied GPX3 and RBP1 genes indicates DNA methylation impact on expression of these tumor suppressors, which could play an important role in myelomagenesis.
Keyword(s): DNA methylation, Gene expression, Tumor suppressor