Our aim was to compare serum levels of selected biological parameters in different phases of multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS) to determine their diagnostic and prognostic potential. A cohort of 234 individuals was assessed for serum levels of hepatocyte growth factor (HGF), syndecan-1/CD(138) (SYN), and osteopontin (OPN). The patients with MM (N = 156) were divided into 3 groups: at the time of diagnosis (N = 45), in relapse/progression (N = 56), and in remission (N = 50). The analysis revealed significant differences of all three parameters in comparison of active and remission phase MM. Moreover, the parameters in active myeloma were significantly higher than in MGUS. Within the comparison of active disease (newly diagnosed and relapsing), there was no significant difference. Similar results were in remission phase MM and MGUS. There was no relationship of pretreatment levels of the parameters to therapeutic response. We conclude that serum levels of HGF, OPN, and SYN correspond to the activity of MM and might become useful in differentiation of MGUS, asymptomatic MM, and overt/symptomatic form of MM. The levels of all three parameters behave accordingly with MM activity. Pretreatment measurement without the assessment of their kinetics, however, has no relationship to therapeutic response.

Department of Internal Medicine 3 Palacky University and University Hospital Olomouc 775 20 Olomouc Czech Republic

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Scudla V, Petrova P, Minarik J, Pika T, Bacovsky J. Analysis of the serum levels of selected biological parameters in monoclonal gammopathy of undetermined significance and different stages of multiple myeloma. Neoplasma. 2011;58(6):499–506. PubMed

Alexandrakis MG, Passam FH, Sfiridaki A, Kandidaki E, Roussou P, Kyriakou DS. Elevated serum concentration of hepatocyte growth factor in patients with multiple myeloma: correlation with markers of disease activity. American Journal of Hematology. 2003;72(4):229–233. PubMed

Andersen NF, Standal T, Nielsen JL, et al. Syndecan-1 and angiogenic cytokines in multiple myeloma: correlation with bone marrow angiogenesis and survival. British Journal of Haematology. 2005;128(2):210–217. PubMed

Saeki Y, Mima T, Ishii T, et al. Enhanced production of osteopontin in multiple myeloma: clinical and pathogenic implications. British Journal of Haematology. 2003;123(2):263–270. PubMed

Seidel C, Lenhoff S, Brabrand S, et al. Hepatocyte growth factor in myeloma patients treated with high-dose chemotherapy. British Journal of Haematology. 2002;119(3):672–676. PubMed

Vacca A, Ribatti D, Roccaro AM, Frigeri A, Dammacco F. Bone marrow angiogenesis in patients with active multiple myeloma. Seminars in Oncology. 2001;28(6):543–550. PubMed

Rajkumar SV, Leong T, Roche PC, et al. Prognostic value of bone marrow angiogenesis in multiple myeloma. Clinical Cancer Research. 2000;6(8):3111–3116. PubMed

Vacca A, Ribatti D, Roncali L, et al. Bone marrow angiogenesis and progression in multiple myeloma. British Journal of Haematology. 1994;87(3):503–508. PubMed

Molina JR, Rajkumar SV. Bone marrow angiogenesis in multiple myeloma: closing in on the loop. Haematologica. 2003;88(2):122–124. PubMed

Sezer O, Niemöller K, Eucker J, et al. Bone marrow microvessel density is a prognostic factor for survival in patients with multiple myeloma. Annals of Hematology. 2000;79(10):574–577. PubMed

Du W, Hattori Y, Yamada T, et al. NK4, an antagonist of hepatocyte growth factor (HGF), inhibits growth of multiple myeloma cells: molecular targeting of angiogenic growth factor. Blood. 2007;109(7):3042–3049. PubMed

Holt RU, Fagerli UM, Baykov V, et al. Hepatocyte growth factor promotes migration of human myeloma cells. Haematologica. 2008;93(4):619–622. PubMed

Sato T, Hakeda Y, Yamaguchi Y, et al. Hepatocyte growth factor is involved in formation of osteoclast-like cells mediated by clonal stromal cells (MC3T3-G2/PA6) Journal of Cellular Physiology. 1995;164(1):197–204. PubMed

Fuller K, Owens J, Chambers TJ. The effect of hepatocyte growth factor on the behaviour of osteoclasts. Biochemical and Biophysical Research Communications. 1995;212(2):334–340. PubMed

Standal T, Abildgaard N, Fagerli UM, et al. HGF inhibits BMP-induced osteoblastogenesis: possible implications for the bone disease of multiple myeloma. Blood. 2007;109(7):3024–3030. PubMed

Pour L, Kovářová L, Buchler T, et al. Evaluation of HGF and endostatin in the bone marrow of patients with multiple myeloma and the effect of peripheral blood admixture. Scripta Medica Facultatis Medicae Universitatis Brunensis Masarykianae. 2009;82(2):123–126.

Seidel C, Børset M, Turesson I, Abildgaard N, Sundan A, Waage A. Elevated serum concentrations of hepatocyte growth factor in patients with multiple myeloma. Blood. 1998;91(3):806–812. PubMed

Sezer O, Jakob C, Eucker J, et al. Serum levels of the angiogenic cytokines basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) in multiple myeloma. European Journal of Haematology. 2001;66(2):83–88. PubMed

Pour L, Svachova H, Adam Z, et al. Pretreatment hepatocyte growth factor and thrombospondin-1 levels predict response to high-dose chemotherapy for multiple myeloma. Neoplasma. 2010;57(1):29–34. PubMed

Šváchová H, Pour L, Almáša M, et al. Concentration of hepatocyte growth factor and thrombospondin predict treatment response in patients with multiple myeloma. Transfuze a Hematologie Dnes. 2010;16(1):30–34.

Colla S, Morandi F, Lazzaretti M, et al. Human myeloma cells express the bone regulating gene Runx2/Cbfa1 and produce osteopontin that is involved in angiogenesis in multiple myeloma patients. Leukemia. 2005;19(12):2166–2176. PubMed

Standal T, Hjorth-Hansen H, Rasmussen T, et al. Osteopontin is an adhesive factor for myeloma cells and is found in increased levels in plasma from patients with multiple myeloma. Haematologica. 2004;89(2):174–182. PubMed

Robbiani DF, Colon K, Ely S, Ely S, Chesi M, Bergsagel PL. Osteopontin dysregulation and lytic bone lesions in multiple myeloma. Hematological Oncology. 2007;25(1):16–20. PubMed

Sfiridaki A, Miyakis S, Pappa C, et al. Circulating osteopontin: a dual marker of bone destruction and angiogenesis in patients with multiple myeloma. Journal of Hematology and Oncology. 2011;4, article 22 PubMed PMC

Yang Y, Yaccoby S, Liu W, et al. Soluble syndecan-1 promotes growth of myeloma tumors in vivo. Blood. 2002;100(2):610–617. PubMed

Purushothaman A, Uyama T, Kobayashi F, et al. Heparanase-enhanced shedding of syndecan-1 by myeloma cells promotes endothelial invasion and angiogenesis. Blood. 2010;115(12):2449–2457. PubMed PMC

Seidel C, Sundan A, Hjorth M, et al. Serum syndecan-1: a new independent prognostic marker in multiple myeloma. Blood. 2000;95(2):388–392. PubMed

Ščudla V, Budíková M, Petrová P, et al. Analysis of serum levels of selected biological parameters in monoclonal gammopathy of undetermined significance and multiple myeloma. Klinicka Onkologie. 2010;23(3):171–181. PubMed