Scientists led by hematologist Jan Kroenke and proteomics expert Philipp Mertins conducted a detailed study of mutations and post-transcriptional changes in tumor cells from over 100 multiple myeloma patients and 38 healthy controls. Their multi-omic analysis included deep tandem mass tag-based quantitative global (phospho)proteomics, RNA sequencing, and nanopore DNA sequencing in 138 patient-derived primary plasma cell malignancies, including treatment-naïve patients with multiple myeloma, plasma cell leukemia, and precancerous monoclonal gammopathy of undetermined significance, as well as healthy controls.
“We found that the (phospho)proteome of malignant plasma cells is highly deregulated compared to healthy plasma cells, determined by both chromosomal alterations and post-transcriptional regulation,” says Kroenke. A prognostic protein signature associated with multiple myeloma malignancy was identified, independent of established risk factors. By integrating functional genetics and single-cell RNA sequencing, we uncovered common and genetic subtype-specific deregulated proteins and signaling pathways in malignant plasma cells that may represent potential targets for (immuno)therapy.
The newly identified proteins and signaling pathways may be the basis for more effective and tolerable treatments, such as CAR-T cell therapy. The scientists have made the data publicly available through interactive, freely available online tools that make the analysis’ complex datasets manageable. Other research groups can easily access the results and use the information to develop new treatments and tests to guide treatment. The first real-world study analyzing multiple myeloma was recently launched in Germany. The European Medicines Agency is facing problems in the field of multiple myeloma, as leading scientists have had conflicts of interest that have kept promising candidates off the market.
