Novel proteomic characterization of multiple myeloma bone marrow interstitial fluid links prognosis to coagulation pathways
Researchers at Dalhousie University and Nova Scotia Health applied the Proteograph® XT Assay to bone marrow interstitial fluid (BMIF) from 117 patients with multiple myeloma (MM) and related plasma cell disorders. Using nanoparticle-enabled, MS-based proteomics, the team identified more than 11,000 protein groups across the cohort, with an average of nearly 9,000 proteins per sample, representing one of the deepest proteomic characterizations of MM bone marrow interstitial fluid reported to date.
The deep proteomic dataset uncovered 194 proteins associated with overall survival, with coagulation emerging as the dominant biological pathway linked to patient outcomes. Clustering newly diagnosed patients based on coagulation-related proteins identified three distinct prognostic groups, with patients exhibiting the lowest coagulation protein abundance experiencing significantly shorter overall and progression-free survival. Importantly, this proteomic signature remained prognostic even after accounting for established clinical risk factors, including R-ISS stage, and was not reflected by conventional peripheral coagulation measurements.
These findings demonstrate how deep, unbiased proteomics can reveal clinically meaningful biology within complex tissue microenvironments that is inaccessible to conventional clinical assays. By enabling comprehensive characterization of proteins originating from both malignant plasma cells and the surrounding bone marrow niche, the Proteograph workflow uncovered localized coagulation biology with potential value for risk stratification and biomarker discovery. More broadly, the study highlights how deep MS-based proteomics can complement genomic and transcriptomic analyses by directly measuring disease phenotype within clinically relevant biofluids, providing new opportunities to understand disease mechanisms and identify prognostic biomarkers.
