ABERRANT DNA METHYLATION-INDUCED GENE INACTIVATION IS ASSOCIATED WITH THE T-CELL LEUKEMIAS DIAGNOSIS AND/OR THERAPY
(Abstract release date: 05/19/16)
EHA Library. Kim E. 06/09/16; 134498; PB1598
Dr. Eun Ju Kim
Contributions
Contributions
Abstract
Abstract: PB1598
Type: Publication Only
Background
Aberrant hypermethylation of tumor suppressor genes is known to play an important role in the development of many tumors, and aberrant DNA hypermethylation was recently identified in hematologic malignancies, where it is thought to hold relevance in leukemogenesis.
Aims
These observations led us to focus on our comprehensive study to examine the prevalence of aberrant promoter methylation in a selected panel of genes that could be potentially involved in T-cell leukemia. In addition to identifying new biomarkers, exploration of methylation patterns could be used to guide T-cell leukemia therapies.
Methods
Here, we used pyrosequencing (a sensitive, easy and effective real-time sequencing-by-synthesis technique) to assess changes in the methylation levels of individual genes between normal peripheral blood (in which they are not normally methylated) and two T-cell keukemia cell lines (in which they are hypermethylated).
Results
We report that there are differences in the DNA methylation patterns seen in normal peripheral blood and two T-cell leukemia cell lines. We identify nine genes (CLEC4E, CR1, DBC1, EPO, HAL-DOA, IGF2, IL12B, ITGA1, and LMX1B) that are significantly hypermethylated in T-cell leukemias cell lines, and suggest that aberrant hypermethylation of these normally unmethylated genes may induce their transcriptional and expressional silencing. Furthermore, we observed that the expression levels of DNMT1 and DNMT3a were significantly decreased by 5-aza-2’-deoxycytidine (5-Aza-dC), which is a demethylation agent known to deplete DNA methyltransferases (DNMTs) in leukemia cancer cells and restore the expression levels of their target genes in Jurkat cells.
Conclusion
Together, our results show that aberrant hypermethylation is an important molecular mechanism in the progression of T-cell leukemias, and thus could prove useful as a prognostic and/or diagnostic marker. Moreover, 5-Aza-dC might be a promising candidate for the treatment of T-cell leukemia.
Session topic: E-poster
Keyword(s): DNA methylation, EPO, Hypermethylation, T cell leukemia
Type: Publication Only
Background
Aberrant hypermethylation of tumor suppressor genes is known to play an important role in the development of many tumors, and aberrant DNA hypermethylation was recently identified in hematologic malignancies, where it is thought to hold relevance in leukemogenesis.
Aims
These observations led us to focus on our comprehensive study to examine the prevalence of aberrant promoter methylation in a selected panel of genes that could be potentially involved in T-cell leukemia. In addition to identifying new biomarkers, exploration of methylation patterns could be used to guide T-cell leukemia therapies.
Methods
Here, we used pyrosequencing (a sensitive, easy and effective real-time sequencing-by-synthesis technique) to assess changes in the methylation levels of individual genes between normal peripheral blood (in which they are not normally methylated) and two T-cell keukemia cell lines (in which they are hypermethylated).
Results
We report that there are differences in the DNA methylation patterns seen in normal peripheral blood and two T-cell leukemia cell lines. We identify nine genes (CLEC4E, CR1, DBC1, EPO, HAL-DOA, IGF2, IL12B, ITGA1, and LMX1B) that are significantly hypermethylated in T-cell leukemias cell lines, and suggest that aberrant hypermethylation of these normally unmethylated genes may induce their transcriptional and expressional silencing. Furthermore, we observed that the expression levels of DNMT1 and DNMT3a were significantly decreased by 5-aza-2’-deoxycytidine (5-Aza-dC), which is a demethylation agent known to deplete DNA methyltransferases (DNMTs) in leukemia cancer cells and restore the expression levels of their target genes in Jurkat cells.
Conclusion
Together, our results show that aberrant hypermethylation is an important molecular mechanism in the progression of T-cell leukemias, and thus could prove useful as a prognostic and/or diagnostic marker. Moreover, 5-Aza-dC might be a promising candidate for the treatment of T-cell leukemia.
Session topic: E-poster
Keyword(s): DNA methylation, EPO, Hypermethylation, T cell leukemia
Abstract: PB1598
Type: Publication Only
Background
Aberrant hypermethylation of tumor suppressor genes is known to play an important role in the development of many tumors, and aberrant DNA hypermethylation was recently identified in hematologic malignancies, where it is thought to hold relevance in leukemogenesis.
Aims
These observations led us to focus on our comprehensive study to examine the prevalence of aberrant promoter methylation in a selected panel of genes that could be potentially involved in T-cell leukemia. In addition to identifying new biomarkers, exploration of methylation patterns could be used to guide T-cell leukemia therapies.
Methods
Here, we used pyrosequencing (a sensitive, easy and effective real-time sequencing-by-synthesis technique) to assess changes in the methylation levels of individual genes between normal peripheral blood (in which they are not normally methylated) and two T-cell keukemia cell lines (in which they are hypermethylated).
Results
We report that there are differences in the DNA methylation patterns seen in normal peripheral blood and two T-cell leukemia cell lines. We identify nine genes (CLEC4E, CR1, DBC1, EPO, HAL-DOA, IGF2, IL12B, ITGA1, and LMX1B) that are significantly hypermethylated in T-cell leukemias cell lines, and suggest that aberrant hypermethylation of these normally unmethylated genes may induce their transcriptional and expressional silencing. Furthermore, we observed that the expression levels of DNMT1 and DNMT3a were significantly decreased by 5-aza-2’-deoxycytidine (5-Aza-dC), which is a demethylation agent known to deplete DNA methyltransferases (DNMTs) in leukemia cancer cells and restore the expression levels of their target genes in Jurkat cells.
Conclusion
Together, our results show that aberrant hypermethylation is an important molecular mechanism in the progression of T-cell leukemias, and thus could prove useful as a prognostic and/or diagnostic marker. Moreover, 5-Aza-dC might be a promising candidate for the treatment of T-cell leukemia.
Session topic: E-poster
Keyword(s): DNA methylation, EPO, Hypermethylation, T cell leukemia
Type: Publication Only
Background
Aberrant hypermethylation of tumor suppressor genes is known to play an important role in the development of many tumors, and aberrant DNA hypermethylation was recently identified in hematologic malignancies, where it is thought to hold relevance in leukemogenesis.
Aims
These observations led us to focus on our comprehensive study to examine the prevalence of aberrant promoter methylation in a selected panel of genes that could be potentially involved in T-cell leukemia. In addition to identifying new biomarkers, exploration of methylation patterns could be used to guide T-cell leukemia therapies.
Methods
Here, we used pyrosequencing (a sensitive, easy and effective real-time sequencing-by-synthesis technique) to assess changes in the methylation levels of individual genes between normal peripheral blood (in which they are not normally methylated) and two T-cell keukemia cell lines (in which they are hypermethylated).
Results
We report that there are differences in the DNA methylation patterns seen in normal peripheral blood and two T-cell leukemia cell lines. We identify nine genes (CLEC4E, CR1, DBC1, EPO, HAL-DOA, IGF2, IL12B, ITGA1, and LMX1B) that are significantly hypermethylated in T-cell leukemias cell lines, and suggest that aberrant hypermethylation of these normally unmethylated genes may induce their transcriptional and expressional silencing. Furthermore, we observed that the expression levels of DNMT1 and DNMT3a were significantly decreased by 5-aza-2’-deoxycytidine (5-Aza-dC), which is a demethylation agent known to deplete DNA methyltransferases (DNMTs) in leukemia cancer cells and restore the expression levels of their target genes in Jurkat cells.
Conclusion
Together, our results show that aberrant hypermethylation is an important molecular mechanism in the progression of T-cell leukemias, and thus could prove useful as a prognostic and/or diagnostic marker. Moreover, 5-Aza-dC might be a promising candidate for the treatment of T-cell leukemia.
Session topic: E-poster
Keyword(s): DNA methylation, EPO, Hypermethylation, T cell leukemia
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