MULTIPLE myeloma (MM) is a bone marrow plasma cell malignancy that remains incurable despite therapeutic advances. A new study, from Charité Universitätsmedizin Berlin, set out to understand the disease better on a molecular level.
Evelyn Ramberger, Charité Universitätsmedizin Berlin, Germany, and colleagues conducted a comprehensive multiomics analysis, including deep tandem mass tag-based quantitative global (phospho)proteomics, RNA sequencing, and nanopore DNA sequencing on 138 primary patient-derived plasma cell malignancies. The study comprised treatment-naive MM, plasma cell leukemia, and the premalignancy monoclonal gammopathy of undetermined significance, along with healthy controls.
The findings revealed that the (phospho)proteome of malignant plasma cells is highly deregulated compared to healthy plasma cells, influenced by both chromosomal alterations and posttranscriptional regulation. A prognostic protein signature associated with aggressive disease was additionally identified, independent of established MM risk factors.
Finally, integration with functional genetics and single-cell RNA sequencing identified deregulated proteins and pathways specific to both general and genetic subtypes of plasma cell malignancies. These findings highlight potential targets for new immunotherapies, marking a significant step forward in understanding and combating this challenging malignancy.
Helena Bradbury, EMJ
Reference
Ramberger E et al. The proteogenomic landscape of multiple myeloma reveals insights into disease biology and therapeutic opportunities. Nat Cancer.
