multiple myeloma; alternative splicing; Proteasome inhibitor resistance; Signaling pathway
Abstract :
[en] Multiple myeloma is the second most common blood cancer, with 50,000 new cases diagnosed annually in Europe. The median survival is about 5 years.
Proteasome inhibitors (PIs) like Bortezomib (BTZ) and Carfilzomib (CFZ) are standard first-line treatments, but resistance often develops. To investigate
MM resistance to PIs, we conducted RNA-seq on BTZ- and CFZ-resistant AMO1 cells versus sensitive cells, analyzing gene expression and splicing
changes. Indeed, it is known that aberrant RNA splicing is key to cancer drug resistance. We identified upregulation of genes related to the Wnt signaling
pathway, potentially altering the expression of proliferation or drug resistance-related genes. Additionally, we observed significant exon skipping events in
FOXM1. It appears that the proportion of FOXM1b isoform is higher in BTZ-resistant cells compared to WT.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Pautet, Léa ; Université de Liège - ULiège > GIGA > GIGA Cancer - Molecular Analysis of Gene Expression
Besse, Lenka; Kantonsspital St Gallen > Experimental Oncology and Hematology, Department of Oncology and Hematology
Besse, Andrej; Kantonsspital St Gallen > Experimental Oncology and Hematology, Department of Oncology and Hematology
Galvan, Bartimée; University Children’s Hospital Zurich > Division of Oncology and Children’s research center
Lafontaine, Denis; Universitée libre de Bruxelles > RNA Molecular Biology
Mottet, Denis ; Université de Liège - ULiège > GIGA > GIGA Cancer - Molecular Analysis of Gene Expression
Language :
English
Title :
Deciphering the molecular mechanisms related to proteasome inhibitor resistance in Multiple Myeloma
