Vnitr Lek 2006, 52(3):232-240

Comparison of serum levels of selected biological parameters in monoclonal gammopathy of undetermined significance and multiple myeloma

V. Ščudla1,*, M. Budíková2, T. Pika1, J. Minařík1, M. Zemanová1, J. Bačovský1, V. Heincová3, Česká myelomová skupina
1 III. interní klinika Lékařské fakulty UP a FN, Olomouc, přednosta prof. MUDr. Vlastimil Ščudla, CSc.
2 Klinika nukleární medicíny Lékařské fakulty UP a FN, Olomouc, přednosta doc. MUDr. Miroslav Mysliveček, CSc.
3 Hematologické a transfuzní oddělení Slezské nemocnice, Opava, přednostka prim. MUDr. Vladimíra Heincová

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.

Keywords: multiple myeloma; monoclonal gammopathy of undetermined significance; angiogennic cytokines; indicators of bone turnover; syndecan-1; sFas

Received: December 14, 2005; Accepted: December 29, 2005; Published: March 1, 2006  Show citation

ACS AIP APA ASA Harvard Chicago Chicago Notes IEEE ISO690 MLA NLM Turabian Vancouver
Ščudla V, Budíková M, Pika T, Minařík J, Zemanová M, Bačovský J, et al.. Comparison of serum levels of selected biological parameters in monoclonal gammopathy of undetermined significance and multiple myeloma. Vnitr Lek. 2006;52(3):232-240.
Download citation

References

  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. Go to original source... Go to PubMed...
  2. Adam Z, Česká myelomová skupina a Myelomová sekce ČHS pro diagnostiku a léčbu mnohočetného myelomu: Diagnostika a léčba mnohočetného myelomu. Transf Hematol dnes 2005; 11(Suppl 1): 3-51.
  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. Go to original source...
  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. Go to original source... Go to PubMed...
  5. Bladé J. On the "Significance" of monoclonal gammopathy of undetermined significance. Mayo Clin Proc 2004; 79: 855-856. Go to original source... Go to PubMed...
  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. Go to original source... Go to PubMed...
  7. Cook G, Dumbar M, Franklin IM. The role of adhesion molecules in multiple myeloma. Acta Haematol 1997; 97: 81-89. Go to original source... Go to PubMed...
  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. Go to original source... Go to PubMed...
  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. Go to original source...
  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. Go to original source... Go to PubMed...
  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. Go to original source...
  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. Go to PubMed...
  13. Durie BGM, Salmon SE, Moon TE. Pretreatment tumour mass, cell kinetics and prognosis in multiple myeloma. Blood 1980; 55: 364-372. Go to original source...
  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. Go to original source... Go to PubMed...
  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. Go to original source... Go to PubMed...
  17. Fonseca R, Barlogie B, Bataille R et al. Genetics and cytogenetics of multiple myeloma: a workshop report. Cancer Res 2004; 64: 1546-1558. Go to original source... Go to PubMed...
  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. Go to original source... Go to PubMed...
  19. Hideshima T, Bergsagel PL, Kuehl MW et al. Advances in biology of multiple myeloma: Clinical applications. Blood 2004; 104: 607-618. Go to original source... Go to PubMed...
  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. Go to original source... Go to PubMed...
  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. Go to original source... Go to PubMed...
  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. Go to original source... Go to PubMed...
  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. Go to original source... Go to PubMed...
  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. Go to original source... Go to PubMed...
  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. Go to original source... Go to PubMed...
  27. Landowski TH, Qu N, Buyuksal I et al. Mutations in the Fas antigen in patients with multiple myeloma. Blood 1997; 90: 4266-4270. Go to original source...
  28. Lauta VM. A review of the cytokine network in multiple myeloma. Cancer 2003; 97: 2440-2452. Go to original source... Go to PubMed...
  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. Go to PubMed...
  31. Nagata S, Golstein P. The Fas death factor. Science 1995; 267: 1449. Go to original source... Go to PubMed...
  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. Go to original source... Go to PubMed...
  34. Pour L, Hájek R, Buchler T et al. Angiogeneze a antiangiogenní terapie u nádorů. Vnitř Lék 2004; 50: 930-938. Go to PubMed...
  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. Go to original source... Go to PubMed...
  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. Go to original source... Go to PubMed...
  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. Go to original source... Go to PubMed...
  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. Go to original source...
  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. Go to original source...
  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. Go to original source...
  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. Go to original source... Go to PubMed...
  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. Go to original source... Go to PubMed...
  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. Go to original source...
  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. Go to original source...
  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. Go to PubMed...
  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. Go to PubMed...
  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. Go to original source... Go to PubMed...
  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. Go to original source...
  52. Vacca A, Ribatti D, Roccaro AM et al. Bone marrow angiogenesis in patients with active multiple myeloma. Sem Oncol 2001; 28: 543-550. Go to original source... Go to PubMed...
  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. Go to original source...
  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. Go to original source... Go to PubMed...
  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. Go to original source... Go to PubMed...
  56. Xu D. Telomerase activity in plasma cell dyscrasias. Br J Cancer 2001; 84: 621-625. Go to original source... Go to PubMed...




Vnitřní lékařství

Madam, Sir,
please be aware that the website on which you intend to enter, not the general public because it contains technical information about medicines, including advertisements relating to medicinal products. This information and communication professionals are solely under §2 of the Act n.40/1995 Coll. Is active persons authorized to prescribe or supply (hereinafter expert).
Take note that if you are not an expert, you run the risk of danger to their health or the health of other persons, if you the obtained information improperly understood or interpreted, and especially advertising which may be part of this site, or whether you used it for self-diagnosis or medical treatment, whether in relation to each other in person or in relation to others.

I declare:

  1. that I have met the above instruction
  2. I'm an expert within the meaning of the Act n.40/1995 Coll. the regulation of advertising, as amended, and I am aware of the risks that would be a person other than the expert input to these sites exhibited


No

Yes

If your statement is not true, please be aware
that brings the risk of danger to their health or the health of others.