{"id":{"repo_id":"aachen","oai_identifier":"oai:publications.rwth-aachen.de:50768"},"canonical_url":"https://search.dev.ndltd.org/etd/aachen/oai:publications.rwth-aachen.de:50768","repository":{"repo_id":"aachen","name":"RWTH Aachen University","base_url":"https://publications.rwth-aachen.de/oai2d"},"display":{"title":"Aberrante DNA-Methylierung des Transkriptionsfaktors C/EBP[alpha] bei akuter myeloischer Leukämie","abstract":"Based on the role of epigenetic changes as an alternative mechansim of transcriptional inactivation of cancer-related genes in hematopoietic malignancies as well as the relevance of CCAAT/enhancer binding protein alpha (C/EBP alpha) in early stages of myeloid differentiation and regulation we investigated the methylation status of the C/EBP alpha promotor region near the transcription start site in acute myelogenous leukemia (AML). Aberrant methylation of the C/EBP alpha promotor region was found in 10/80 (12,5%) primary samples from AML in the French-American-British (FAB)-subtypes M1, M2, M4, M4eo und M5. Moreover hypermethylation was detected exclusively in cytogenetically favorable and intermediate risk groups. Clinical trials with demethylating agents as 5-aza-2’-desoxycytidine (DAC) und 5-azacytidin (AZA) provided promising findings in therapy of acute leukemias and myelodysplastic syndrome (MDS). We showed, that in hematopoietic tumor cell lines, CpG island hypermethylation of the proximal C/EBP alpha promotor region was associated with transcriptional silencing, and treatment with the demethylating agent DAC resulted in C/EBP alpha reexpression and promotor demethylation. C/EBP alpha has been shown to regulate cell cycle progression through inhibition of cyclin-dependent-kinase (CDK) 2 and 4. Therefore we investigated a possible relationship between the methylation patterns of C/EBP alpha and another cell cycle regulator p15, which is a common target for epigenetic inactivation in AML. Our data indicate an inverse correlation between aberrant methylation of C/EBP alpha and the negative cell cycle regulator p 15. This context should be evaluated in more extensive trials. The investigation of pathophysiological coherency between aberrant C/EBP alpha methylation and C/EBP alpha-mutation could be interesting concerning genetic and epigenetic mechanisms. In addition to that C/EBP alpha may add to the list of epigenetically silenced tumor suppressor genes with a well-defined biological role in leukemogenesis that could be used for disease stratification as well as a therapeutic target.","abstract_html":"Based on the role of epigenetic changes as an alternative mechansim of transcriptional inactivation of cancer-related genes in hematopoietic malignancies as well as the relevance of CCAAT/enhancer binding protein alpha (C/EBP alpha) in early stages of myeloid differentiation and regulation we investigated the methylation status of the C/EBP alpha promotor region near the transcription start site in acute myelogenous leukemia (AML). Aberrant methylation of the C/EBP alpha promotor region was found in 10/80 (12,5%) primary samples from AML in the French-American-British (FAB)-subtypes M1, M2, M4, M4eo und M5. Moreover hypermethylation was detected exclusively in cytogenetically favorable and intermediate risk groups. Clinical trials with demethylating agents as 5-aza-2’-desoxycytidine (DAC) und 5-azacytidin (AZA) provided promising findings in therapy of acute leukemias and myelodysplastic syndrome (MDS). We showed, that in hematopoietic tumor cell lines, CpG island hypermethylation of the proximal C/EBP alpha promotor region was associated with transcriptional silencing, and treatment with the demethylating agent DAC resulted in C/EBP alpha reexpression and promotor demethylation. C/EBP alpha has been shown to regulate cell cycle progression through inhibition of cyclin-dependent-kinase (CDK) 2 and 4. Therefore we investigated a possible relationship between the methylation patterns of C/EBP alpha and another cell cycle regulator p15, which is a common target for epigenetic inactivation in AML. Our data indicate an inverse correlation between aberrant methylation of C/EBP alpha and the negative cell cycle regulator p 15. This context should be evaluated in more extensive trials. The investigation of pathophysiological coherency between aberrant C/EBP alpha methylation and C/EBP alpha-mutation could be interesting concerning genetic and epigenetic mechanisms. In addition to that C/EBP alpha may add to the list of epigenetically silenced tumor suppressor genes with a well-defined biological role in leukemogenesis that could be used for disease stratification as well as a therapeutic target.","abstract_has_math":false,"creators":["Cabral do Ó, Nicole Tânia"],"institution":"Publikationsserver der RWTH Aachen University","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":["Galm, Oliver"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2009,"date_issued":"2009","date_published":"2009","updated_at":"2026-07-30T19:40:25Z","subjects":["info:eu-repo/classification/ddc/610","Akute myeloische Leukämie","Epigenetik","Zellzyklus","Medizin","DNA Methylierung","C/EBP","transkriptionale Inaktivierung","DNA methylation","acute myelogenous leukemia","epigenetics","transcriptional silencing"],"languages":["ger"],"rights":["info:eu-repo/semantics/openAccess"],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["https://publications.rwth-aachen.de/search?p=id:%22RWTH-CONV-113297%22"],"render_values":[{"text":"https://publications.rwth-aachen.de/search?p=id:%22RWTH-CONV-113297%22","href":"https://publications.rwth-aachen.de/search?p=id:%22RWTH-CONV-113297%22","code":true}]}]},"links":{"outbound_url":"https://publications.rwth-aachen.de/record/50768","outbound_label":"Repository record","outbound_source":"dc:identifier"},"source_record":{"url":"https://publications.rwth-aachen.de/oai2d?verb=GetRecord&metadataPrefix=oai_dc&identifier=oai%3Apublications.rwth-aachen.de%3A50768","prefix":"oai_dc"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Galm, Oliver"]},{"key":"dc:creator","label":"Author","values":["Cabral do Ó, Nicole Tânia"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:coverage","label":"Dc Coverage","values":["DE"]},{"key":"dc:date","label":"Dc Date","values":["2009"]},{"key":"dc:publisher","label":"Institution","values":["Publikationsserver der RWTH Aachen University"]},{"key":"dc:relation","label":"Dc Relation","values":["info:eu-repo/semantics/altIdentifier/urn/urn:nbn:de:hbz:82-opus-27489"]},{"key":"dc:type","label":"Dc Type","values":["info:eu-repo/semantics/doctoralThesis","info:eu-repo/semantics/publishedVersion"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["info:eu-repo/classification/ddc/610","Akute myeloische Leukämie","Epigenetik","Zellzyklus","Medizin","DNA Methylierung","C/EBP","transkriptionale Inaktivierung","DNA methylation","acute myelogenous leukemia","epigenetics","transcriptional silencing"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["ger"]},{"key":"dc:rights","label":"Dc Rights","values":["info:eu-repo/semantics/openAccess"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://publications.rwth-aachen.de/record/50768","https://publications.rwth-aachen.de/search?p=id:%22RWTH-CONV-113297%22"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Based on the role of epigenetic changes as an alternative mechansim of transcriptional inactivation of cancer-related genes in hematopoietic malignancies as well as the relevance of CCAAT/enhancer binding protein alpha (C/EBP alpha) in early stages of myeloid differentiation and regulation we investigated the methylation status of the C/EBP alpha promotor region near the transcription start site in acute myelogenous leukemia (AML). Aberrant methylation of the C/EBP alpha promotor region was found in 10/80 (12,5%) primary samples from AML in the French-American-British (FAB)-subtypes M1, M2, M4, M4eo und M5. Moreover hypermethylation was detected exclusively in cytogenetically favorable and intermediate risk groups. Clinical trials with demethylating agents as 5-aza-2’-desoxycytidine (DAC) und 5-azacytidin (AZA) provided promising findings in therapy of acute leukemias and myelodysplastic syndrome (MDS). We showed, that in hematopoietic tumor cell lines, CpG island hypermethylation of the proximal C/EBP alpha promotor region was associated with transcriptional silencing, and treatment with the demethylating agent DAC resulted in C/EBP alpha reexpression and promotor demethylation. C/EBP alpha has been shown to regulate cell cycle progression through inhibition of cyclin-dependent-kinase (CDK) 2 and 4. Therefore we investigated a possible relationship between the methylation patterns of C/EBP alpha and another cell cycle regulator p15, which is a common target for epigenetic inactivation in AML. Our data indicate an inverse correlation between aberrant methylation of C/EBP alpha and the negative cell cycle regulator p 15. This context should be evaluated in more extensive trials. The investigation of pathophysiological coherency between aberrant C/EBP alpha methylation and C/EBP alpha-mutation could be interesting concerning genetic and epigenetic mechanisms. In addition to that C/EBP alpha may add to the list of epigenetically silenced tumor suppressor genes with a well-defined biological role in leukemogenesis that could be used for disease stratification as well as a therapeutic target."]},{"key":"dc:source","label":"Dc Source","values":["Aachen : Publikationsserver der RWTH Aachen University III, 88 S. : Ill., graph. Darst. (2009). = Aachen, Techn. Hochsch., Diss., 2009"]},{"key":"dc:title","label":"Title","values":["Aberrante DNA-Methylierung des Transkriptionsfaktors C/EBP[alpha] bei akuter myeloischer Leukämie"]}]}],"canonical_facts":{"dc:contributor":["Galm, Oliver"],"dc:coverage":["DE"],"dc:creator":["Cabral do Ó, Nicole Tânia"],"dc:date":["2009"],"dc:description":["Based on the role of epigenetic changes as an alternative mechansim of transcriptional inactivation of cancer-related genes in hematopoietic malignancies as well as the relevance of CCAAT/enhancer binding protein alpha (C/EBP alpha) in early stages of myeloid differentiation and regulation we investigated the methylation status of the C/EBP alpha promotor region near the transcription start site in acute myelogenous leukemia (AML). Aberrant methylation of the C/EBP alpha promotor region was found in 10/80 (12,5%) primary samples from AML in the French-American-British (FAB)-subtypes M1, M2, M4, M4eo und M5. Moreover hypermethylation was detected exclusively in cytogenetically favorable and intermediate risk groups. Clinical trials with demethylating agents as 5-aza-2’-desoxycytidine (DAC) und 5-azacytidin (AZA) provided promising findings in therapy of acute leukemias and myelodysplastic syndrome (MDS). We showed, that in hematopoietic tumor cell lines, CpG island hypermethylation of the proximal C/EBP alpha promotor region was associated with transcriptional silencing, and treatment with the demethylating agent DAC resulted in C/EBP alpha reexpression and promotor demethylation. C/EBP alpha has been shown to regulate cell cycle progression through inhibition of cyclin-dependent-kinase (CDK) 2 and 4. Therefore we investigated a possible relationship between the methylation patterns of C/EBP alpha and another cell cycle regulator p15, which is a common target for epigenetic inactivation in AML. Our data indicate an inverse correlation between aberrant methylation of C/EBP alpha and the negative cell cycle regulator p 15. This context should be evaluated in more extensive trials. The investigation of pathophysiological coherency between aberrant C/EBP alpha methylation and C/EBP alpha-mutation could be interesting concerning genetic and epigenetic mechanisms. In addition to that C/EBP alpha may add to the list of epigenetically silenced tumor suppressor genes with a well-defined biological role in leukemogenesis that could be used for disease stratification as well as a therapeutic target."],"dc:identifier":["https://publications.rwth-aachen.de/record/50768","https://publications.rwth-aachen.de/search?p=id:%22RWTH-CONV-113297%22"],"dc:language":["ger"],"dc:publisher":["Publikationsserver der RWTH Aachen University"],"dc:relation":["info:eu-repo/semantics/altIdentifier/urn/urn:nbn:de:hbz:82-opus-27489"],"dc:rights":["info:eu-repo/semantics/openAccess"],"dc:source":["Aachen : Publikationsserver der RWTH Aachen University III, 88 S. : Ill., graph. Darst. (2009). = Aachen, Techn. 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