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Longitudinal comprehensive transcriptome analyses to unravel disease persistence and evolution in MPN

Subject Area Hematology, Oncology
Term since 2024
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 517204983
 
Based on the hypothesis that altered epigenetic RNA modification, splicing and aberrant non-coding RNA expression lead to the disruption of key regulatory pathways in MPN pathogenesis, we will comprehensively study altered gene expression, epigenetic RNA modifications, alternatively spliced isoforms as well as the expression of non-coding RNAs. Based on comprehensive analyses of distinct longitudinal MPN cohorts, intra- and inter-individual comparisons will allow us to determine tumor escape and disease persistence mechanisms. Finally, we aim to perform an ultra-high content single-cell multi-omics approach in selected patients to capture clonal heterogeneity, which might allow us to understand MPN persistence as well as mechanisms of disease progression. For all aims, data analysis will include the integration of comprehensive genomic and clinical information, which is available within the German Study Group (GSG) MPN-BioRegistry, followed by technical and functional validation of findings. Ultimately, this project will identify biomarkers and resistance mechanisms that provide the basis for developing novel therapeutic strategies that could prevent progression/leukemic transformation.
DFG Programme Research Units
 
 

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