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AuthorStolze, Ina Susannedc.contributor.author
Date of accession2016-03-14T13:40:50Zdc.date.accessioned
Available in OPARU since2016-03-14T13:40:50Zdc.date.available
Year of creation2005dc.date.created
AbstractCEBPA (CCAAT/enhancer binding protein alpha) is a transcription factor which plays an important role in the differentiation of myeloid progenitor cells into granulocytes. The purpose of this thesis was the analysis of the incidence, the molecular characteristics and the prognostic relevance of CEBPA-mutations in patients with acute myeloid leukaemia (AML). The entire CEBPA-gene was sequenced in diagnostic samples of 122 AML-patients aged 16 to 60 years, homogeneously treated on a protocol of the AML Study Group Ulm. The focus lay on the group of patients with normal karyotype, which is classified as intermediate risk. Within this group of 84 patients, 13 % had a CEBPA-mutation, 7 % had more than one CEBPA-mutation. Different types of mutations could be identified: N-terminal loss-of-function-mutations (in 6 %) affect the transactivation-domains and lead to the synthesis of a shorter dominant-negative CEBPA-isoform. Mutations of the C-terminal basic-region-leucine-zipper domain were found as frameshift- (in 4 %) or in-frame-mutations (in 5 %). They are predicted to impair the binding of CEBPA to the DNA. N-terminal loss-of-function-mutations and C-terminal in-frame mutations often coincided; they were localized on different alleles. There was a striking accumulation of the FAB-subtypes M1 and M2 among the patients with a CEBPA-mutation. The data of this work flew into a retrospective study with 236 AML-patients with normal cytogenetics to assess the prognostic relevance of CEBPA-mutations. Patients with a CEBPA-mutation showed a significantly longer remission duration (p = .01) and overall survival (p = .05). The CEBPA-mutation-status was an independent prognostic factor. In the future, the analysis of the CEBPA-mutation-status may improve the risk stratification in AML by identifying patients with a favourable outcome within the clinically heterogeneous group of patients with normal cytogenetics and take influence on new risk adapted therapy protocols.dc.description.abstract
Languagededc.language.iso
PublisherUniversität Ulmdc.publisher
LicenseStandard (Fassung vom 03.05.2003)dc.rights
Link to license texthttps://oparu.uni-ulm.de/xmlui/license_v1dc.rights.uri
KeywordCCAAT/enhancer binding protein alphadc.subject
KeywordRisikostratifizierungdc.subject
KeywordRisk stratificationdc.subject
Dewey Decimal GroupDDC 610 / Medicine & healthdc.subject.ddc
LCSHTranscription factorsdc.subject.lcsh
MeSHCEBPA protein, humandc.subject.mesh
MeSHLeukemia, myeloid, acutedc.subject.mesh
TitleCEBPA-Mutationen bei jüngeren Erwachsenen mit akuter myeloischer Leukämie und normalem Karyotypdc.title
Resource typeDissertationdc.type
DOIhttp://dx.doi.org/10.18725/OPARU-716dc.identifier.doi
URNhttp://nbn-resolving.de/urn:nbn:de:bsz:289-vts-56935dc.identifier.urn
GNDAkute myeloische Leukämiedc.subject.gnd
GNDTranskriptionsfaktordc.subject.gnd
FacultyMedizinische Fakultätuulm.affiliationGeneral
Date of activation2006-08-22T19:55:06Zuulm.freischaltungVTS
Peer reviewneinuulm.peerReview
Shelfmark print versionZ: J-H 11.239 ; W: W-H 9.353uulm.shelfmark
DCMI TypeTextuulm.typeDCMI
VTS-ID5693uulm.vtsID
CategoryPublikationenuulm.category


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