Differences in the proteome within extracellular vesicles between premalignant and malignant plasma cell disorders

Area of Science:

• Hematology
• Oncology
• Biochemistry

Background:

• Monoclonal gammopathy of undetermined significance (MGUS) precedes multiple myeloma (MM).
• Early identification of MGUS patients progressing to MM requires novel biomarkers.
• Plasma-derived extracellular vesicles (EVs) are potential sources of MM biomarkers.

Purpose of the Study:

• To isolate and analyze small EVs (SEVs) and large EVs (LEVs) from MGUS and MM patients.
• To identify protein biomarkers within EVs for MM diagnosis and prognosis.
• To investigate the role of EVs in MM pathogenesis.

Main Methods:

• Isolation of SEVs and LEVs from peripheral blood plasma of MGUS and MM patients using size exclusion chromatography.
• Proteomic analysis of isolated EVs using a label-free workflow.
• Quantification and comparison of protein expression between MGUS and MM patient-derived EVs.

Main Results:

• 2055 proteins identified in SEVs and 2794 in LEVs.
• Transferrin receptor (CD71) was upregulated in MM-derived EVs (SEVs and LEVs) and showed prognostic significance.
• Serum amyloid A proteins (SAA1, SAA2, SAA4) were highly upregulated in SEVs from MM patients.
• CD40 expression was higher in LEVs from MM patients compared to MGUS patients.

Conclusions:

• Successful isolation of SEVs and LEVs from plasma of patients with plasma cell disorders.
• Identified protein biomarkers (CD71, SAA, CD40) in EVs with potential diagnostic and prognostic value for MM.
• Demonstrated the feasibility of using EV proteomics for understanding MM biology.