Líffræðifélag Íslands - biologia.is
Líffræðiráðstefnan 2023
Höfundar / Authors: Díana Ágústsdóttir, Stamatia Maria Rapti and Erna Magnúsdóttir
Starfsvettvangur / Affiliations: Erna’s Magnusdottir lab, Department of Anatomy and Biomedical Science, School of Health Sciences, University of Iceland.
Kynnir / Presenter: Díana Ágústsdóttir
Waldenstrom Macroglobulinemia (WM) is a rare non-Hodgkin lymphoma, characterized by over-secretion of IgM and overexpression of lymphocytes and lymphoplasmacytoid cells. Treatments today do not eliminate non-dividing plasma cells, which makes WM still incurable. This shows that WM needs more understanding of pathways associated with the disease. This leads us to investigate the transcriptional factor BLIMP1, expressed in plasma-cell development. Our laboratory findings show that knockdown (KD) of BLIMP1 cells had a 40-fold increase in the expression of Activation-induced cytidine deaminase (AID) and an increase in the accumulation of double-stranded breaks (DSB). This leads us to further investigate the mechanism of the AID protein, a key regulator in B-cell differentiation, mutating the Ig-locus. The project's aims are to address the role of BLIMP1 and AID in DNA damage in different cell cycle phases. Our lab has engineered a miRNA sequence to target PRDM1 transcript to KD endogenous BLIMP1 in the presence of doxycycline in our RPCI-WM1 cell line. Furthermore, we engineered the cells into two cell lines containing lentiviral cassettes encoding a destabilization domain and GFP, fused with or without BLIMP1. We have seen promising results in the connection of the BLIMP1 KD, DSBs and the cell cycle. In our future directions we will look at whether these DSB are part-associated with AID expression, thus when we increase the AID will it lead to an increase in DSB and vice versa