Publication Date:
2018-11-29
Description:
Background: Multiple myeloma (MM) is characterized by clinical and biological heterogeneity, translating to variable outcome. High International Staging System (ISS), high risk cytogenetics, elevated LDH, poor response to novel drugs or extramedullary-disease (EMD) are associated to poor prognosis. Exosomes (EXO) are extra vesicular particles implicated in intercellular communication. Exosomal cargo has recently been studied as prognostic factors in cancer. MM-EXO may act as biomarkers of disease aggressiveness and potentially be used for better stratification of high risk disease in the clinical setting as liquid biopsies. Aims: To characterize peripheral blood (PB) and bone marrow aspirates (BM) EXO in MM and MGUS patients versus healthy donors (HD) and to analyze its potential use as a prognostic biomarker. Methods: EXO were isolated from PB and BM samples by ultracentrifugation. EXO protein quantity (EXOcargo) was determined by the ratio between total quantity of proteins and the total number of exosomes. Comparisons among groups of patients (MM, MGUS) and HD were made regarding EXO total protein cargo (PB and BM). Results: MM patients revealed 5x times higher EXOcargo in PB (ug/EXO) when compared to MGUS patients (p=0.007, n=15 MM and n=8 MGUS); MM median 2.34 (1.08-6.5) ug/EXO versus MGUS median 0.51 (0.29-1.04) ug/EXO. There was no differences regarding the EXOcargo between the MGUS and HD (n=6, HD median 0.88 (0.57-1.83)ug/EXO). In BM, MM EXOcargo was also higher than in MGUS: MM 2.09 (0.49-3.85)ug/EXO versus MGUS 0.53 (0.21-0.831)ug/EXO. Analyzing the patients with higher EXOcargo, we found that patients with EMD (n=4) are among the ones with higher circulating exosomal protein cargo (median 5.76 (4.36-7.95). A positive correlation in EXOcargo between PB and BM in MM and MGUS (Spearman r=0.85; p〈 0.0001) was found. We also studied circulating EXOcargo at response evaluation (T2) compared to EXOcargo before MM treatment (T1): patients with deeper response had significant lower EXOcargo (CR T2 median 0.85 (0.65-1.35) p
Print ISSN:
0006-4971
Electronic ISSN:
1528-0020
Topics:
Biology
,
Medicine
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