Líffræðifélag Íslands - biologia.is
Líffræðiráðstefnan 2025
Erindi/veggspjald / Talk/poster V12
Höfundar / Authors: Björgvin Ægir Elisson (1), Erna Magnúsdóttir (1), Adrián López García de Lomana (2)
Starfsvettvangur / Affiliations: 1. EM-Group - Háskóli Íslands - Læknagarður, Vatnsmýrarvegur 16, 2. BioMedical Center - Vatnsmýrarvegur 16
Kynnir / Presenter: Björgvin Ægir Elisson
Waldenström Macroglobulinemia (WM) is a rare, indolent, and incurable B-cell malignancy. The only drug federally accepted to treat WM is ibrutinib, a Bruton’s Tyrosine Kinase inhibitor (BTKi) that inhibits BTK in the NF-κβ pathway which WM relies on for survival. Enhancers are cis-regulatory regions in the genome that regulate transcription when bound by a transcription factor. Enhancers can regulate distal genes through topologically associated domains (TADs) that form gene loops and bring enhancers in range of faraway genes. WM patients are susceptible to developing ibrutinib resistance and some genomic mutations that mediate ibrutinib resistance have been identified in ~40% of resistant WM cases. However, the epigenetic effects on ibrutinib resistance are unknown but enhancers have been identified as oncogenic in other tumour types. We had a cell culture of the BCWM.1 cell-line which we made ibrutinib resistant with continuous drug exposure over 6 months and extracted sensitive and resistant triplicated samples for sequencing. We will conduct a thorough CUT&RUN bioinformatics pipeline to investigate the epigenetic mediation of drug resistance in WM, do DEG analysis and perform motif analysis for possible TFBS. 1294 DEGs were identified between conditions with Sleuth and 1358 DEGs with DESeq2. The Enrichr database revealed the top 10 associated transcription factors to the DEGs. We will present this along with preliminary CUT&RUN analysis.