Despite advances in the understanding of cancer biology, most patients with acute myeloid leukemia (AML) still die of their disease. Improving risk-stratification and identifying new targets are important steps towards personalized medicine and outcome improvement. MicroRNAs, short non-coding RNAs that hybridize to their target messenger RNAs (mRNAs) and repress the expression of the encoded proteins, are known to be involved in physiological processes like cellular differentiation, proliferation and cell survival but also play an essential role in cancer, including AML.
In this thesis we demonstrated that higher expression of a single microRNA miR-181a was associated with clinical outcome in cytogenetically normal AML (CN AML) patients. In multivariable models, higher expression of miR-181a was associated with achievement of complete remission (CR), with longer disease-free (DFS) and overall survival (OS) even in consideration of other validated prognostic clinical and molecular variables. Measurement of pretreatment levels of this microRNA may improve risk-stratification for AML patients. A genome-wide gene-expression signature gave biological insights into miR-181a associated AML, and provides a basis for further functional studies. Furthermore, as higher miR-181a expression associated with improved treatment response, increasing miR-181a levels by delivering synthetic miR-181a or by agents increasing endogenous levels of this microRNA in AML blasts may represent a novel and personalized therapeutic approach in AML.:Bibliografische Beschreibung 1
Vorbemerkung / Preliminary Remarks 2
Referat / Abstract 3
Einführung / Introduction 4
Publication 13
Zusammenfassung / Conclusion 31
Ausgewählte Publikation / Selected Publication 38
Komplette Publikationsliste / Complete List of Publications 39
Lebenslauf / Curriculum Vitae 46
Erklärung über die eigenständige Abfassung der Arbeit 50
Danksagung / Acknowledgements 51
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:12245 |
| Date | 14 November 2013 |
| Creators | Schwind, Sebastian |
| Contributors | Niederwieser, Dietger, NA - anonymisiert, NA - anonymisiert, Universität Leipzig |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | doc-type:doctoralThesis, info:eu-repo/semantics/doctoralThesis, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
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