Contributions
Abstract: PB1637
Type: Publication Only
Session title: Myeloma and other monoclonal gammopathies - Biology & Translational Research
Background
Multiple myeloma is biologically heterogenic disease with wide spectrum of genetic and epigenetic changes. Global hypomethylation and gene-specific promoter hypermethylation are supposed to be included in mechanism in myelomagenesis.
Aims
The study is focused on global DNA methylation assessment and its relationship to methylation level of promoter and 1. exon sequences of PDLIM4 and CDKN2B genes.
Methods
The set of 94 un-sorted samples of bone marrow aspirate from patients with MGUS and multiple myeloma (MM) in different disease stages (smoldering myeloma, MM diagnosis, MM remission, MM relapse), were examined in our study. An informed consent from all patient was obtained. For determination of the global DNA methylation level, the Luminometric Methylation Analysis (LUMA) was newly implemented. Methylation analysis of particular gene sequences was performed by bisulfite pyrosequencing.
Results
While CDKN2B gene methylation level was generally low (median between 4 % and 5,5 % in first exon and between 1 % and 4 % in promotor), the increased promoter PDLIM4 methylation was determined in newly diagnosed patients with multiple myeloma (median 19 %). The highest global DNA methylation level was detected in MGUS samples (76,5 %), and its gradual decreasing during myeloma progression was observed (medians: 73,1 % in smoldering myeloma, 72,5 % in MM diagnosis and 69,4% MM relapse). In the subgroup of myeloma remission patients, the level of global DNA methylation showed an upward trend (median 73,4 %).
Conclusion
The LUMA method proved to be an effective procedure and ease to perform. Our results of global DNA methylation assessment are in accordance with literature data relating to haemato-oncological malignancies. Further, the use of a bone marrow of the un-sorted cell population could be an advantage of the method procedure. Moreover, our data support an important role of the PDLIM4 gene in the onset and progression of multiple myeloma disease. In contrast with some other studies, we did not confirm any methylation changes in CDKN2B gene analysed sequences, which indicates its unmethylated state.
Keyword(s): Methylation, Myeloma
Abstract: PB1637
Type: Publication Only
Session title: Myeloma and other monoclonal gammopathies - Biology & Translational Research
Background
Multiple myeloma is biologically heterogenic disease with wide spectrum of genetic and epigenetic changes. Global hypomethylation and gene-specific promoter hypermethylation are supposed to be included in mechanism in myelomagenesis.
Aims
The study is focused on global DNA methylation assessment and its relationship to methylation level of promoter and 1. exon sequences of PDLIM4 and CDKN2B genes.
Methods
The set of 94 un-sorted samples of bone marrow aspirate from patients with MGUS and multiple myeloma (MM) in different disease stages (smoldering myeloma, MM diagnosis, MM remission, MM relapse), were examined in our study. An informed consent from all patient was obtained. For determination of the global DNA methylation level, the Luminometric Methylation Analysis (LUMA) was newly implemented. Methylation analysis of particular gene sequences was performed by bisulfite pyrosequencing.
Results
While CDKN2B gene methylation level was generally low (median between 4 % and 5,5 % in first exon and between 1 % and 4 % in promotor), the increased promoter PDLIM4 methylation was determined in newly diagnosed patients with multiple myeloma (median 19 %). The highest global DNA methylation level was detected in MGUS samples (76,5 %), and its gradual decreasing during myeloma progression was observed (medians: 73,1 % in smoldering myeloma, 72,5 % in MM diagnosis and 69,4% MM relapse). In the subgroup of myeloma remission patients, the level of global DNA methylation showed an upward trend (median 73,4 %).
Conclusion
The LUMA method proved to be an effective procedure and ease to perform. Our results of global DNA methylation assessment are in accordance with literature data relating to haemato-oncological malignancies. Further, the use of a bone marrow of the un-sorted cell population could be an advantage of the method procedure. Moreover, our data support an important role of the PDLIM4 gene in the onset and progression of multiple myeloma disease. In contrast with some other studies, we did not confirm any methylation changes in CDKN2B gene analysed sequences, which indicates its unmethylated state.
Keyword(s): Methylation, Myeloma