De Boussac H, Machura A, Steer A, Kassambara A, Gely M, Chemlal D, Gourzones C, Requirand G, Robert N, Vincent L, Herbaux C, Bruyer A, Moreaux J. P844: Characterization of Multiple Myeloma Cell Lines With Acquired-Resistance to Proteasome Inhibitors Highlights a Link Between Resistance and Metabolic Deregulation. Hemasphere. 2022. Download the PDF
Summary of the Study
This study investigates mechanisms of acquired resistance to proteasome inhibitors (PIs) in multiple myeloma (MM) using in vitro models and multi-omics profiling.
Six Bortezomib-resistant MM cell lines (BR-HMCLs) were developed by long-term exposure to escalating PI doses.
BR-HMCLs displayed:
- Elevated resistance to Bortezomib, Carfilzomib, and Ixazomib
- No cross-resistance to other agents (IMiDs, melphalan, dexamethasone)
Genomic and transcriptomic profiling revealed:
- 40 key mutations, including one in PSMB5, directly impairing PI binding
- Upregulation of glycolytic enzymes (e.g., ALDOC, HK1, ENO3, PDK1/3)
- Changes in solute carrier transporters and xenobiotic response genes
Functional Seahorse assays demonstrated:
- Upon Bortezomib challenge, resistant cells showed increased mitochondrial respiration and glycolysis
- Parental cells showed reduced metabolic activity under the same conditions
In this study, Alboukadel Kassambara led the implementation of whole genome sequencing and transcriptomic analysis pipelines, enabling the identification of resistance-associated mutations and transcriptional reprogramming in proteasome inhibitor-resistant MM cell lines.
Citation
Publication: In Hemasphere (Poster Abstract)
Date: June 23, 2022
Type: Poster Presentation
PDF: Download the PDF
Scientific Contributions
Here are more scientific abstracts authored or co-authored by Alboukadel Kassambara. These contributions span computational biology, bioinformatics, biostatistics, machine learning, and multi-omics, with a focus on immuno-oncology and translational research.
