Table 2. Results of the different... | American Society of Hematology

Table 2.

Results of the different biomarkers studies in MM using different EVs

Type	Samples	Methodology∗	Biomarker	Impact	Reference
Protein
MV	N=2 MM	Serum UC Immunoblotting	Monoclonal Ig (FLC)	Detectable in MM MVs	84
exo	N=10 5T33MM mice	Blood Exoquick Immunocapture	Monoclonal Ig	Detectable in MM EVs earlier than M protein	85
MV	N=8 ND, 26PR, 18CR, 14PD, 18HD	Plasma UC FC	CD138	Higher in MM vs HD, correlates to MM progression	86
MV	N=115ND, 48CR, 20HD	Blood/BM UC FC	CD138	Higher in MM vs HD, correlates to MM progression	87
MV	N=14ND, 30PR, 12CR, 18PD, 24HD	Plasma UC FC	CD138/P-gp+/CD34	High CD138-P-pg+CD34+EV count associated with unresponsiveness to treatment	88
MV	N=61ND, 5PD, 29HD	Plasma UC FC	CD138	Higher in MM vs HD, correlation with bone disease	39
MV	N=12 ND, 28 HD	Serum UC FC	CD38	Higher in MM vs HD	89
MV	N=27MM, 11 MGUS, 14 SMM	BM plasma UC FC	CD38	Higher in MM vs MGUS and SMM	43
MV	N=10 MM, 20 ND	Serum Bench centrifugation FC	CD138/CD38	Single and double positive EVs higher in MM vs HD Double positive correlate with tumor burden	90
exo	N=8 ND,16 PD 8 MGUS, 16 HD	Plasma Exoquick FC	CD163/CD206	Higher in MM vs MGUS, HD and RR	93
exo	N=233 ND (of which 32 immunoblot), 13 HD	Serum UC Elisa/immunoblot	CD44	Higher in MM vs HD	91
RNA
exo	N=156 ND, 5 HD	Serum Exoquick Small RNAseq	Let-7b, let-7e, miR-106a, miR-106b, miR-155, miR-16, miR-17, miR-18a, miR-20a	Lower in MM vs HD, let-7b and miR-18a predictors for PFS and OS	96
exo	N=3 MM, 18 HD	UC qRT-PCR	miR-155	Lower in MM vs HD	97
exo	N=20 MM, 20S MM, 16 HD	Serum Exoquick qRT-PCR	let-7c-5p, let-7d-5p, miR-185-5p, miR-103a-3p, miR20a-5p	Lower in MM vs SMM and HD	98
			miR4505 and miR4741	Higher in MM vs SMM and HD
exo	N=48 ND, 16 HD	Serum Exoquick Microarray/qRT-PCR	let-7c-5p, let-7d-5p, miR-140-3p, miR-185-5p, and miR-425-5p	Lower in MM vs HD, negative correlation with disease progression and tumor burden	99
exo	N=115 MM (73 responder, 42 non-responder)	Serum UC miRNA array	MiR-17-5p, miR-20a-5p, miR- 15a-5p and miR-16-5p	Lower in bortezomib resistant patients	101
exo	N=5 bz resistant, 5 bz sensitive MM	Serum UC RNAseq	482 lncRNA and 2099 mRNA	FFAR1 and SP9 were increased, potential diagnostic marker HIST1H2BG and ITIH2 were decreased in resistance	102
exo	N=122 MM, 54 HD	Serum Exoquick qRT-PCR	circ-Myc	Higher in MM vs HD, correlated to 17p deletion and translocation of t(4;14)	103
exo	N=25 MM, 5 HD	Serum Exoquick RNA seq/qRT-PCR	265 upregulated and 787 downregulated circRNAs (MM vs HD)	chr2:2744228–2 744 407+correlated to peripheral neuropathy	104
exo	N=20 MM, 5 HD	Serum Exoquick RNA seq/qRT-PCR	circATP10A	Prognostic potential, correlated to vascular endothelial growth factor B levels	106
exo	N=20 MM, 5 HD	Serum Exoquick qRT-PCR	circ-G042080	Predictor myocard damage	105
exo	N=56 MM, 49 MGUS, 36 HD	Serum miCURY exosome isolation kit lncRNA array	PRINS	Negative correlation with PC in BM	100

Type	Samples	Methodology∗	Biomarker	Impact	Reference
Protein
MV	N=2 MM	Serum UC Immunoblotting	Monoclonal Ig (FLC)	Detectable in MM MVs	84
exo	N=10 5T33MM mice	Blood Exoquick Immunocapture	Monoclonal Ig	Detectable in MM EVs earlier than M protein	85
MV	N=8 ND, 26PR, 18CR, 14PD, 18HD	Plasma UC FC	CD138	Higher in MM vs HD, correlates to MM progression	86
MV	N=115ND, 48CR, 20HD	Blood/BM UC FC	CD138	Higher in MM vs HD, correlates to MM progression	87
MV	N=14ND, 30PR, 12CR, 18PD, 24HD	Plasma UC FC	CD138/P-gp+/CD34	High CD138-P-pg+CD34+EV count associated with unresponsiveness to treatment	88
MV	N=61ND, 5PD, 29HD	Plasma UC FC	CD138	Higher in MM vs HD, correlation with bone disease	39
MV	N=12 ND, 28 HD	Serum UC FC	CD38	Higher in MM vs HD	89
MV	N=27MM, 11 MGUS, 14 SMM	BM plasma UC FC	CD38	Higher in MM vs MGUS and SMM	43
MV	N=10 MM, 20 ND	Serum Bench centrifugation FC	CD138/CD38	Single and double positive EVs higher in MM vs HD Double positive correlate with tumor burden	90
exo	N=8 ND,16 PD 8 MGUS, 16 HD	Plasma Exoquick FC	CD163/CD206	Higher in MM vs MGUS, HD and RR	93
exo	N=233 ND (of which 32 immunoblot), 13 HD	Serum UC Elisa/immunoblot	CD44	Higher in MM vs HD	91
RNA
exo	N=156 ND, 5 HD	Serum Exoquick Small RNAseq	Let-7b, let-7e, miR-106a, miR-106b, miR-155, miR-16, miR-17, miR-18a, miR-20a	Lower in MM vs HD, let-7b and miR-18a predictors for PFS and OS	96
exo	N=3 MM, 18 HD	UC qRT-PCR	miR-155	Lower in MM vs HD	97
exo	N=20 MM, 20S MM, 16 HD	Serum Exoquick qRT-PCR	let-7c-5p, let-7d-5p, miR-185-5p, miR-103a-3p, miR20a-5p	Lower in MM vs SMM and HD	98
			miR4505 and miR4741	Higher in MM vs SMM and HD
exo	N=48 ND, 16 HD	Serum Exoquick Microarray/qRT-PCR	let-7c-5p, let-7d-5p, miR-140-3p, miR-185-5p, and miR-425-5p	Lower in MM vs HD, negative correlation with disease progression and tumor burden	99
exo	N=115 MM (73 responder, 42 non-responder)	Serum UC miRNA array	MiR-17-5p, miR-20a-5p, miR- 15a-5p and miR-16-5p	Lower in bortezomib resistant patients	101
exo	N=5 bz resistant, 5 bz sensitive MM	Serum UC RNAseq	482 lncRNA and 2099 mRNA	FFAR1 and SP9 were increased, potential diagnostic marker HIST1H2BG and ITIH2 were decreased in resistance	102
exo	N=122 MM, 54 HD	Serum Exoquick qRT-PCR	circ-Myc	Higher in MM vs HD, correlated to 17p deletion and translocation of t(4;14)	103
exo	N=25 MM, 5 HD	Serum Exoquick RNA seq/qRT-PCR	265 upregulated and 787 downregulated circRNAs (MM vs HD)	chr2:2744228–2 744 407+correlated to peripheral neuropathy	104
exo	N=20 MM, 5 HD	Serum Exoquick RNA seq/qRT-PCR	circATP10A	Prognostic potential, correlated to vascular endothelial growth factor B levels	106
exo	N=20 MM, 5 HD	Serum Exoquick qRT-PCR	circ-G042080	Predictor myocard damage	105
exo	N=56 MM, 49 MGUS, 36 HD	Serum miCURY exosome isolation kit lncRNA array	PRINS	Negative correlation with PC in BM	100

bz, bortezomib; CR, complete response; exo, exosomes; FC, flow cytometry; HD, healthy donors; MV, microvesicles; ND, newly diagnosed MM; PC, plasma cells; PD, progressive disease; PR, partial response; RR, relapsed/refractory; UC, ultracentrifugation.

∗

Methodology shown in order of source, isolation technique, and characterization technique.

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