Περίληψη
Παράγοντες που συμμετέχουν στην προσκόλληση των πλασματοκυττάρων στο μυελικό υπόστρωμα ή προάγουν τη μετανάστευση αυτών, και κυτοκίνες-ρυθμιστές του οστικού μεταβολισμού παίζουν πιθανώς σημαντικό ρόλο στην παθογένεια του πολλαπλού μυελώματος. Σκοπός: Ο προσδιορισμός των επιπέδων s-synd-1, MIP-1α, sRANKL, OPG, ΙGF-1, VEGF και TGF-β1 στον ορό ασθενών με πολλαπλούν μυέλωμα (ΠΜ) κατά τη διάγνωση και η διερεύνηση της σχέσης τους με παραμέτρους της νόσου και με την επιβίωση. Ασθενείς και μέθοδοι: Μελετήθηκαν 102 ασθενείς με ΠΜ, 18 άτομα με μονοκλωνική γαμμαπάθεια αδιευκρίνιστης σημασίας (ΜGUS) και 27 φυσιολογικοί μάρτυρες (ΦΜ). Φυλάχτηκαν σε όλους τους ασθενείς και ΦΜ κατεψυγμένοι οροί. Τα επίπεδα των υπό μελέτη διαλυτών παραγόντων και κυτοκινών προσδιορίστηκαν με ELISA σύμφωνα με τις οδηγίες του κατασκευαστή. Αποτελέσματα: Στους ΦΜ, τους ασθενείς με ΠΜ και με MGUS τα διάμεσα επίπεδα ήταν 15 ng/ml (7-64), 64 ng/ml (7-3500) και 16.5 ng/ml (10-175) για το s-synd-1 ορού, 28 pg/ml (15-60), 32 pg ...
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Cytokines involved in plasma cells adhesion and migration to the bone marrow and factors regulating bone metabolism might play an important role in multiple myeloma (MM) biology. Aim: To determine serum levels of s-synd-1, MIP-1α, OPG, sRANKL, IGF-1, VEGF and TGF-β1 in untreated myeloma patients and to correlate them with parameters of disease activity and prognosis. Patients and Methods: Frosen sera from 102 untreated MM patients, 18 subjects with monoclonal gammopathy of undetermined significance (MGUS) and 27 healthy individuals (HI) were studied. Cytokines were determined by commercially available ELISA. Results: In HI, median s-synd-1 was 15 ng/ml (7-64), MIP-1α 28 pg/ml (15-60), OPG 1600 pg/ml (450-8000), sRANKL 6 pg/ml (2.6-12.4), IGF-1 96 ng/ml (46-210), VEGF 110 pg/ml (10-300) and TGF-β1 57500 pg/ml (30000-110000). In MM patients, pretreatment median s-synd-1 was 64 ng/ml (7-3500), MIP-1α 32 pg/ml (14-100), OPG 3100 pg/ml (820-25000), sRANKL 3.75 pg/ml (1.6-200), IGF-1 86 ng ...
Cytokines involved in plasma cells adhesion and migration to the bone marrow and factors regulating bone metabolism might play an important role in multiple myeloma (MM) biology. Aim: To determine serum levels of s-synd-1, MIP-1α, OPG, sRANKL, IGF-1, VEGF and TGF-β1 in untreated myeloma patients and to correlate them with parameters of disease activity and prognosis. Patients and Methods: Frosen sera from 102 untreated MM patients, 18 subjects with monoclonal gammopathy of undetermined significance (MGUS) and 27 healthy individuals (HI) were studied. Cytokines were determined by commercially available ELISA. Results: In HI, median s-synd-1 was 15 ng/ml (7-64), MIP-1α 28 pg/ml (15-60), OPG 1600 pg/ml (450-8000), sRANKL 6 pg/ml (2.6-12.4), IGF-1 96 ng/ml (46-210), VEGF 110 pg/ml (10-300) and TGF-β1 57500 pg/ml (30000-110000). In MM patients, pretreatment median s-synd-1 was 64 ng/ml (7-3500), MIP-1α 32 pg/ml (14-100), OPG 3100 pg/ml (820-25000), sRANKL 3.75 pg/ml (1.6-200), IGF-1 86 ng/ml (13-260), VEGF 275 pg/ml (8-4000) and TGF-β1 61500 pg/ml (1350-99000). In MGUS, median s-synd-1 was 16.5 ng/ml (10-175), MIP-1α 35 pg/ml (17-149), OPG 2500 pg/ml (1500-6200), sRANKL 3.8 pg/ml (3.2-5.6), IGF-1 86 ng/ml (50-190), VEGF 540 pg/ml (250-1700) and TGF-β1 68250 pg/ml (29400-90000). Differences between HI and MM patients levels and between MGUS and MM patients levels were both significant for s-synd-1 (p<0.001 and 0.01 respectively). Differences between HI and MM patients and between HI and MGUS were as well significant for OPG (p<0.001 and 0.04 respectively) and VEGF (p=0.001 and p<0.001 respectively). No statistical significant difference was observed between HI, MGUS and MM patients with regard to MIP-1α, sRANKL, IGF-1 and TGF-β1 levels. Overall survival was decreased in patients with elevated serum s-synd-1 levels (p=0.009). There was a trend for longer survival in patients with OPG levels lower than median (p=0.06), serum MIP-1α levels had a weak impact, while serum sRANKL, IGF-1, VEGF and TGF-β1 levels had no impact. In multivariative analysis, s-synd-1 was an independent prognostic factor of survival. Further analysis of survival of patients stratified according to the ISS system showed a difference in survival within groups according to s-synd-1 levels (mainly for stage 1 and 2). Conclusions: Serum s-synd-1 levels at diagnosis constitute an independent prognostic factor of survival, able to further differentiate patients within the ISS stages. In our experience, there was a trend for shorter survival in patients with elevated OPG or MIP-1α levels but sRANKL, IGF-1, VEGF and TGF-β1 levels had no impact.
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