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The prognostic Impact of microRNA-181a expression levels in patients with cytogenetically normal acute myeloid leukemia

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.

Identiferoai:union.ndltd.org:DRESDEN/oai:qucosa.de:bsz:15-qucosa-130542
Date06 January 2014
CreatorsSchwind, Sebastian
ContributorsUniversität Leipzig, Innere Medizin, Prof. Dr. med. Dietger Niederwieser, NA - anonymisiert NA - anonymisiert
PublisherUniversitätsbibliothek Leipzig
Source SetsHochschulschriftenserver (HSSS) der SLUB Dresden
LanguageEnglish
Detected LanguageEnglish
Typedoc-type:doctoralThesis
Formatapplication/pdf

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