Serum Soluble Syndecan-1 Levels Correlate with Erythropoietin and Inversely with Hemoglobin Levels in Untreated Anaemic Myeloma Patients: Possible Role of Syndecan-1 in the Mechanisms of Chronic Anaemia.

Impaired erythropoiesis with inappropriate erythropoietin (EPO) production is seen in about 40% of symptomatic multiple myeloma (MM) patients at diagnosis and worsens during terminal refractory disease. Up-regulation of proinflammatory and proapoptotic factors, namely TNF-alpha, INF-gamma, TGF-beta1, FAS-Ligand and TRAIL are involved in the pathogenesis of defective erythroid maturation. The involvement of these factors in the progression of MM has been studied and no correlation was found for TNF-alpha, INF-gamma and TGF-beta1, while it was shown that the up-regulation of FAS-L/TRAIL in MM cells contributes to MM aggressiveness. Increased soluble syndecan-1 (s-synd-1) serum levels have been shown to constitute an adverse prognostic factor for survival in MM. Furthermore at least 3 studies, including ours, also found a negative correlation of s-synd-1 levels with hemoglobin. The purpose of this study was to investigate the correlations between s-synd-1, hemoglobin (Hb), endogenous EPO levels and other parameters of disease in anaemic MM patients before any treatment including rHu-EPO administration. 41 MM patients (19 males and 22 females) with variable degree of anaemia (Hb <13.5 g/dl for men and <12.5 g/dlfor women) were studied. Median Hb was 10.5 g/dl (range 6.9–13.5); 32% had Hb below 10 g/dl. Median age was 68y. 7 patients had Durie and Salmon stage I, 21 stage II and 13 stage III. Serum EPO levels were determined by RIA and s-synd by ELISA (Diaclone Research, Besancon, France) in frozen sera of MM patients and 24 healthy individuals. Normal serum EPO levels range from 4.9 to 52 mU/ml in our laboratory. Median s-synd-1 was 36 ng/ml (9–75) in healthy individuals.The median value of EPO levels in MM patients was 40.1 mU/ml (7.2–313) and of s-synd-1 160 ng/ml (26–3500). Serum EPO levels correlated as expected with Hb (Spearman’s rho -0.223, p=0.14), creatinin (Spearman’s rho -0.32, p=0.04) but also with s-synd-1 (Spearman’s rho 0.33, p=0.03). Serum EPO did not correlate either with parameters reflecting disease mass such as beta2microglobulin (Spearman’s rho −0.19, p=0.90) and percentage of bone marrow infiltration (Spearman’s rho 0.118, p=0.48) or CRP (Spearman’s rho −0.189, p=0.29) that reflects proinflammatory cytokines’ activity. Our results in addition to the fact that s-synd-1 levels inversely correlate with Hb levels, suggest that s-synd-1 may be involved in the mechanisms leading to chronic anemia in multiple myeloma. Further studies are needed to confirm these findings.