Líffræðifélag Íslands
Líffræðiráðstefnan 2015
Erindi/veggspjald / Talk/poster V78
Kimberley J Anderson (1), Jón Þór Bergþorsson (2,3), Margrét S Steinarsdóttir (4), Sigurður Y. Kristinsson (3,5,6), Erna Magnusdóttir (1).
1. Biomedical Centre, Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Iceland, 2. Stem Cell Research Unit, Biomedical Centre, Department of Anatomy, Faculty of Medicine, University of Iceland, 3. Department of Haematology, Landspitali University Hospital, Iceland, 4. Chromosome Laboratory, Department of Genetics and Molecular Medicine, Landspitali University Hospital, Iceland, 5. Faculty of Medicine, University of Iceland, 6. Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden
Kynnir / Presenter: Kimberley J Anderson
Tengiliður / Corresponding author: Kimberley J Anderson (kimberl@hi.is)
Multiple myeloma (MM) is an incurable plasma cell malignancy derived from pre-malignant monoclonal gammopathy of undetermined significance (MGUS). Little is understood about the drivers of malignant transformation at the MGUS to MM transition. We hypothesise that transcriptional enhancer networks regulated by long non-coding (lnc)RNAs act as layers of coordinated transcriptional control, and underlie cellular and molecular changes in this disease. New techniques in low cell number next generation sequencing allow unprecedented use of plasma cells isolated directly from the bone marrow of MGUS and MM patients. This study will utilise total RNA sequencing and histone-ChIP sequencing of patient CD138+ cells to identify transcriptional enhancers and lncRNAs differentially active between MGUS and MM. The identified enhancers and lncRNAs will be computationally characterised, defining sequence signatures as well as genetic variations. Finally, functional analyses will be performed for the identified regulatory elements, using CRISPR knockout and chromosome conformation capture, as well as investigations into the role of the enhancers and lncRNAs in the progression to signal independence in MM. With this study, we hope to uncover lncRNA-enhancer transcriptional networks regulating MM disease progression.