Comparison of serum levels of selected biological parameters in monoclonal gammopathy of undetermined significance and multiple myeloma
Authors:
V. Ščudla 1; M. Budíková 2; T. Pika 1; J. Minařík 1; M. Zemanová 1; J. Bačovský 1; V. Heincová 3; Česká Myelomová Skupina
Authors‘ workplace:
III. . interní klinika Lékařské fakulty UP a FN, Olomouc, přednosta prof. MUDr. Vlastimil Ščudla, CSc.
1; Klinika nukleární medicíny Lékařské fakulty UP a FN, Olomouc, přednosta doc. MUDr. Miroslav Mysliveček, CSc.
2; Hematologické a transfuzní oddělení Slezské nemocnice, Opava, přednostka prim. MUDr. Vladimíra Heincová
3
Published in:
Vnitř Lék 2006; 52(3): 232-240
Category:
Original Contributions
Overview
Purpose of study:
The study focuses on evaluation of differences in serum levels of selected biological indicators in monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM), primarily from the viewpoint of potential asset to clinical practice.
Patients and methodology:
The analyse set of 96 patients consisted of 30 individuals with MGUS and 66 patients with MM examined in the context of the disease diagnosis before therapy commencement. Serum levels of the assessed parameters were examined with the help of radio-enzymatic method (thymidinkinase), radioimmunoanalysis (β2-micro-globulin, ICTP, PINP), enzymoimmunoessay method (sIL-6R, sVCAM-1, sICAM-1, sOPG and sRANKL) and the technique of quantitative sandwich enzymatic immunoessay (sHGF, sVEGF, bFGF, syndecan-1/CD138 and sFas). Statistical examination was performed by Pearson and Fischer test, χ2-test, or nonparametric U-test pursuant to Mann-Whitney (p < 0,05).
Results:
Statistically significant differences were found between MGUS and MM in the case of serum level comparisons of sIL- 6R (p = 0.02), ICTP (p = 0.001), sHGF (p = 0.001) and syndecan-1/sCD138 (p = 0.001), while no statistically significant differences were present in the case of sVCAM-1, sICAM-1, PINP, sOPG, sVEGF and sFas. During the analysis of frequency of occurrence of abnormal values in the MM and MGUS groups, significant differences were found not only in the case of standard parameters, such as β2-microglobulin, thymidinkinase, creatinin and albumin, but also in the case of sIL-6R, ICTP, sHGF and syndecan-1, but not in comparisons of the levels of sVCAM-1, sICAM-1, PINP, sOPG, sVEGF and sFas. Attempts at examination of serum levels of sRANKL and soluble form of bFGF failed as too low values were measured.
Conclusion:
The analysis of behaviour of the 10 parameters, mostly intimately related to biological properties of clonal plasmatic cells or to changes of microclimate of bone marrow, effectively contributed to distinction between MGUS and MM only in the case of serum levels of sIL-6R, ICTP, sHGF and syndecan-l (sCD138), i.e. indicators with demonstrable relevance for MM prognosis assessment.
Key words:
multiple myeloma – monoclonal gammopathy of undetermined significance – angiogennic cytokines – indicators of bone turnover – syndecan-1 – sFas
Sources
1. Abildgaard N, Bentzen SM, Nielsen JL et al. Serum markers of bone metabolism in multiple myeloma: Prognostic value of the carboxy-terminal telopeptide of type I collagen (ICTP). Brit J Haematol 1997; 96: 103-110.
2. Adam Z, Česká myelomová skupina a Myelomová sekce ČHS pro diagnostiku a léčbu mnohočetného myelomu: Diagnostika a léčba mnohočetného myelomu. Transf Hematol dnes 2003; 9(Suppl 1): 3-33.
3. Bataille R, Chappard D, Basle MF. Quantifiable excess of bone resorption in monoclonal gammapothy is an early symptom of malignancy: A prospective study of 87 bone biopsies. Blood 1996; 87: 4762-4769.
4. Bataille R, Jourdan M, Zhang XG et al. Serum levels of interleukin 6, a potent myeloma cell growth factor, as a reflect of disease severity in plasma cell dyscrasias. J Clin Invest 1989; 84: 2008-2011.
5. Bladé J. On the „Significance“ of monoclonal gammopathy of undetermined significance. Mayo Clin Proc 2004; 79: 855-856.
6. Cesana C, Klersy C, Barbarano L et al. Prognostic factors for malignant transformation in monoclonal gammopathy of undetermined significance and smoldering multiple myeloma. J Clin Oncol 2002; 20: 1625-1634.
7. Cook G, Dumbar M, Franklin IM. The role of adhesion molecules in multiple myeloma. Acta Haematol 1997; 97: 81-89.
8. Corso A, Dovio A, Rusconi C et al. Osteprotegerin serum levels in multiple myeloma and MGUS patients compared with age-and sex-matched healthy controls. Leukemia 2004; 18: 1555-1557.
9. Dankbar B, Padró T, Leo R et al. Vascular endothelial growth factor and interleukin-6 in paracrine tumor-stromal cell interactions in multiple myeloma. Blood 2000; 95: 2630-2636.
10. Dhodapkar MV, Kelly T, Theus A et al. Elevated levels of shed syndecan-1 correlate with tumour mass and decreased matrix metalloproteinase-9 activity in the serum of patients with multiple myeloma. Brit J Haematol 1999; 99: 368-371.
11. Dhodapkar MV, Abe E, Theus A et al. Syndecan-1 is a multifunctional regulator of myeloma pathobiology: control of tumor cell survival, growth, and bone cell differentiation. Blood 1998; 91: 2679-2688.
12. Di Raimondo F, Azzaro MP, Palumbo GA et al. Angiogenic factors in multiple myeloma: higher levels in bone marrow than in peripheral blood. Haematologica 2000; 85: 800-805.
13. Durie BGM, Salmon SE, Moon TE. Pretreatment tumour mass, cell kinetics and prognosis in multiple myeloma. Blood 1980; 55: 364-372.
14. Durie BGM, Waxman AD, D´Agnolo A et al. Advances in the diagnosis and staging of multiple myeloma. Multiple Myeloma 2004; April 22-24, Torino: 75-77.
15. Ely SA, Knowles DM. Expression of CD56/neural cell adhesion molecule correlates with the presence of lytic bone lesions in multiple myeloma and distinguishes myeloma from monoclonal gammopathy of undetermined significance and lymphomas with plasmacytoid differentiation. Am J Pathol 2002; 160: 1293-1299.
16. Faid L, Van Riet I, De Waele M et al. Adhesive interactions between tumour cells and bone marrow stromal elements in human multiple myeloma. Eur J Haematol 1996; 57: 349-358.
17. Fonseca R, Barlogie B, Bataille R et al. Genetics and cytogenetics of multiple myeloma: a workshop report. Cancer Res 2004; 64: 1546-1558.
18. Giuliani N, Calla S, Rizzoli V. New insight in the mechanism of osteoclast activation and formation in multiple myeloma: Focus on the receptor activator of NF kB ligand (RANKL). Exp Hematol 2004; 32: 685-691.
19. Hideshima T, Bergsagel PL, Kuehl MW et al. Advances in biology of multiple myeloma: Clinical applications. Blood 2004; 104: 607-618.
20. Cheng J, Zhon T, Liu C et al. Protection from Fas-mediated apoptosis by a soluble form of the Fas molecule. Science 1995; 263: 1759-1761.
21. International Myeloma Working Group. Criteria for the classification of monoclonal gammopathies, multiple myeloma and related disorders: a report of the International Myeloma Working Group. Br J Haematol 2003; 121: 749-757.
22. Kawano MM, Huang N, Tanaka H et al. Homotypic cell aggregations of human myeloma cells with ICAM-1 and LFA-1 molecules. Brit J Haematol 1991; 79: 538-548.
23. Kraj M, Centkowski P, Kruk B. Osteoprotegerin and sRANKL serum levels in multiple myeloma patients. Haematol J 2003; 4: S157.
24. Kyle RA, Rajkumar V. Monoclonal gammopathies of undetermined significance: a review. Immunol Rev 2003; 194: 112-139.
25. Kyle RA, Therneau TM, Rajkumar SV et al. A long-term study of prognosis in monoclonal gammopathy of undetermined significance. N Engl J Med 2002; 346: 564-569.
26. Kyrtsonis MC, Dedoussis G, Zervas C et al. Soluble interleukin-6 receptor (sIL-6R), a new prognostic factor in multiple myeloma. Brit J Haematol 1966; 93: 398-400.
27. Landowski TH, Qu N, Buyuksal I et al. Mutations in the Fas antigen in patients with multiple myeloma. Blood 1997; 90: 4266-4270.
28. Lauta VM. A review of the cytokine network in multiple myeloma. Cancer 2003; 97: 2440-2452.
29. Maisnar V, Toušková M, Tichý M et al. The significance of soluble CD138 in diagnosis of monoclonal gammopathies. Neoplasma 2006; (manuscript).
30. Maisnar V, Toušková M, Malý J et al. Význam vybraných laboratorních ukazatelů pro diferenciální diagnostiku a sledování aktivity mnohočetného myelomu. Vnitř Lék 2002; 48: 290-297.
31. Nagata S, Golstein P. The Fas death factor. Science 1995; 267: 1449.
32. Ocqueteau M. Immunophenotypic characterization of plasma cells from monoclonal gammopathy of undetermined significance patients: implications for the differential diagnosis between MGUS and multiple myeloma. Am J Pathol 1998; 152: 1655-1665.
33. Paliton M, Terpos E, Anagnostopoulos A et al. Role of receptor activator of nuclear factor - kappa B ligand (RANKL), osteoprotegerin and macrophage protein 1-alpha (MIP-1a) in monoclonal gammopathy of undetermined significance (MGUS). Brit J Haematol 2004; 126: 686-689.
34. Pour L, Hájek R, Buchler T et al. Angiogeneze a antiangiogenní terapie u nádorů. Vnitř Lék 2004; 50: 930-938.
35. Rajkumar SV, Kyle RA, Therneau TM et al. Presence of monoclonal free light chains in the serum predicts risk of progression in monoclonal gammopathy of undetermined significance. Brit J Haematol 2004; 127: 308-310.
36. Rajkumar SV. Bone marrow angiogenesis in 400 patients with monoclonal gammopathy of undetermined significance, multiple myeloma, and primary amyloidosis. Clin Cancer Res 2002; 8: 2210-2216.
37. Roux S, Meignin V, Quillard J et al. RANK and RANKL expression in multiple myeloma. Brit J Haematol 2002; 117: 86-92.
38. Seidel C, Hjertner O, Abildgaard N et al. Nordic Myeloma Study Group serum osteoprotegerin levels are reduced in patients with multiple myeloma with lytic bone disease. Blood 2001; 98: 2269-2271.
39. Seidel C, Sundan A, Hjorth M et al. Serum syndecan-1: a new independent prognostic marker in multiple myeloma. Blood 2000; 95: 388-392.
40. Seidel C, Borset M, Turesson I et al. For the Nordic Myeloma Study Group. Elevated serum concentrations of hepatocyte growth factor in patients with multiple myeloma. Blood 1998; 91: 806-812.
41. Seidel C, Borset M, Hjertner O et al. High levels of soluble syndecan-1 in myeloma-derived bone marrow: modulation of hepatocyte growth factor activity. Blood 2000; 96: 3139-3146.
42. 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. Eur J Haematol 2001; 66: 83-88.
43. Sezer O, Niemöller K, Jakob C et al. Bone marrow microvessel density is a prognostic factor for survival in patients with multiple myeloma. Ann Hematol 2000; 79: 574-577.
44. Shima Y, Nishimoto N, Ogata A et al. Myeloma cells express Fas antigen/APO-1 (CD95) but only some are sensitive to anti-Fas antibody resulting in apoptosis. Blood 1995; 85: 757-764.
45. Stasi R, Brunetti M, Parma A et al. The prognostic value of soluble interleukin-6 receptor in patients with multiple myeloma. Cancer 1998; 82: 1860-1866.
46. Ščudla V, Bačovský J, Papajík T et al. Tymidinkináza séra u mnohotného myelomu. I. Vztah k vybraným laboratorním ukazatelům nemoci. Vnitř Lék 1994; 40: 151-156.
47. Ščudla V, Kubalová D, Bačovský J et al. Příspěvek k vyšetření solubilního receptoru interleukinu-6 v séru u mnohočetného myelomu. Čas Lék Čes 1996; 135: 719-722.
48. Ščudla V, Budíková M, Bačovský J et al. Vztah hladin solubilních cytoadhezivních molekul VCAM-1 a ICAM-1 k vybraným klinickým a laboratorním ukazatelům mnohočetného myelomu. Vnitř Lék 1999; 45: 583-590.
49. Špička I, Cieslar P, Procházka B et al. Prognostické faktory a markery aktivity u mnohočetného myelomu. Čas Lék Čes 2001; 139: 208-212.
50. Terpos E, Szydlo R, Apperley JF et al. Soluble receptor activator of nuclear factor kappaB ligand - osteoprotegerin ratio predicts survival in multiple myeloma: proposal for a novel prognostic index. Blood 2003; 102: 1064-1069.
51. Urashima M, Chen BP, Chen S et al. The development of a model for the homing of multiple myeloma cells to human bone marrow. Blood 1997; 90: 754-765.
52. Vacca A, Ribatti D, Roccaro AM et al. Bone marrow angiogenesis in patients with active multiple myeloma. Sem Oncol 2001; 28: 543-550.
53. Vacca A, Ribatti D, Presta M et al. Bone marrow neovascularization, plasma cell angiogenic potential, and matrix metalloproteinase-2 secretion parallel progression of human multiple myeloma. Blood 1999; 93: 3064-3073.
54. Vejlgaard T, Abildgaard N, Jans H et al. Abnormal bone turnover in monoclonal gammopathy of undetermined significance: analyses of type I collagen telopeptide, osteocalcin, bone-specific alkaline phosphatase and propeptides of type I and type III procollagens. Eur J Haematol 1997; 58: 104-108.
55. Witzig TE, Kimlinger T, Stenson M et al. Syndecan-1 expression on malignant cells from the blood and marrow of patients with plasma cell proliferative disorders and B-cell chronic lymphocytic leukemia. Leuk Lymphoma 1998; 31: 167-175.
56. Xu D. Telomerase activity in plasma cell dyscrasias. Br J Cancer 2001; 84: 621-625.
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