Líffræðifélag Íslands - biologia.is
Líffræðiráðstefnan 2025
Erindi/veggspjald / Talk/poster E24
Höfundar / Authors: Stamatia-Maria Rapti (1), Diana Augustdottir (1), Zarko Urosevic (1), Erna Magnusdottir (1)
Starfsvettvangur / Affiliations: (1) Department of Anatomy and Biomedical Science, School of Health Sciences, University of Iceland.
Kynnir / Presenter: Stamatia-Maria Rapti
Waldenström Macroglobulinemia (WM) is an incurable B-cell lymphoma with phenotypic heterogeneity, ranging from B-cells to plasma cells. BLIMP1, a transcription factor, is critical for plasma cell differentiation. To study its role in WM, we use the RPCI-WM1 cell line with a doxycycline-inducible BLIMP1 knockdown (KD) via microRNA and a Shield-1-regulated overexpression (OE) system, using a Destabilisation Domain EGFP-BLIMP1. The Shield-1 synthetic molecule enables the rapid manipulation of BLIMP1 levels, allowing the assessment of its direct targets via profiling nascent transcripts. As a control (NTC), a microRNA cell line without a target was used. Our experiments reveal an inverse correlation between BLIMP1 levels and double-strand breaks (DSB), particularly outside S-phase. BLIMP1 OE reduced DSBs by 12.5%, BLIMP1 KD increased DSBs by 10.5%, leading to cell death by day six. Cell cycle analysis showed BLIMP1 KD led to a 15% increase in cells in G1, a 62% decrease in S-phase, and 3-fold increase in apoptotic cells compared to NTC. BLIMP1 OE had the opposite effect, with 22% fewer cells in G1 and 26% increase in S-phase compared to NTC. These results suggest BLIMP1 drives cell cycle progression and WM cell survival. However, prolonged OE of BLIMP1 slows the cell cycle and reduces cell count. Overall, our findings underscore BLIMP1’s key role in WM biology.