Líffræðifélag Íslands - biologia.is
Líffræðiráðstefnan 2025
Erindi/veggspjald / Talk/poster V9
Höfundar / Authors: Julia Suchecka, Erna Magnúsdóttir
Starfsvettvangur / Affiliations: Vatnsmýrarvegur 16 - Læknagarður, Faculty of Medicine, School of Health Sciences, University of Iceland
Kynnir / Presenter: Julia Suchecka
Waldenström’s macroglobulinemia (WM) is a rare lymphoproliferative B- cell disorder characterized by bone marrow infiltration of lymphoplasmacytic B cells and IgM monoclonal gammopathy. Ibrutinib, a BTK inhibitor, is used in treatment but resistance often occurs. Enhancers are DNA elements that increase promoter function and we hypothesize that changes in enhancer activity drive ibrutinib resistance in WM. To analyze this we established resistant and sensitive RPCI-WM1 cells. Resistance was induced by a six-month process of exposing cells to increasing ibrutinib concentrations with a final concentration of 24 μM. The cells were used for CUT&RUN chromatin profiling and next-generation sequencing to map histone modifications (H3K4me1, H3K27ac, H3K4me3, H3K27me3). Peaks will be classified into enhancers, super-enhancers and promoters and enriched transcription factor motifs will be determined. RNA sequencing will identify differentially expressed genes in resistant vs sensitive cells, allowing links to identified enhancers. We’ll also test the role of transcription factors showing motif enrichment in resistance-associated enhancers and upregulation in resistant cells by inducing expression in sensitive cells and assessing changes in resistance. This poster presents results from differential expression analysis and initial findings from enhancer analysis. In summary, we expect to find gene regulation mechanisms contributing to resistance.