Skip to content
Research Article Open access CC BY 4.0

Bone Marrow Mast Cell Density Correlates with Circulating Biomarkers of Bone Disease in Multiple Myeloma

Rodanthi Vyzoukaki, Maria Devetzoglou, Constantina A. Pappa, Andreas N. Antonakis, Samer Masud, Anastasia Papadopoulou, George Tsirakis, Michael G. Alexandrakis

Journal of Advances in Medicine and Medical Research · pp. 1–10 · Published 16 Apr 2016

10.9734/BJMMR/2016/25402

Abstract

Aims: There is increased mast cell density (MCD) in multiple myeloma (MM) bone marrow (BM) that is correlated with advanced disease stage. Mast cells (MCs) produce various mediators promoting MM growth and bone metabolism. The aim of this study was to evaluate whether BM MCD correlates with markers of bone metabolism, such as circulating levels of osteoprotegerin (OPG), soluble receptor activator of nuclear factor-κB ligand (sRANKL), osteopontin (OPN) and macrophage inflammatory protein-1 alpha (MIP-1 alpha). Study Design: This is a cross-sectional study. Place and Duration of Study: Department of Medicine, University of Crete, Department and Laboratory of Haematology, University Hospital of Heraklion, Department of Haematology and Internal Medicine, Venizelion Hospital of Heraklion, Department of Haematology, General Hospital of Chania, between January 2010 and December 2014. Methodology: All parameters were analyzed by ELISA. We studied 56 active MM patients (32 males, 24 females) and 20 healthy controls. According to ISS 14 patients were in stage I, 22 in stage II and 20 in stage III. MCs were highlighted in BM immunohistochemically, using monoclonal antibody to MC tryptase. Results: All values were higher in active MM patients compared to healthy subjects (p<0.001 for all cases). OPG was decreasing in advanced stages (p= 0.018), whereas all other values were in parallel with ISS disease stages (p<0.001 for all cases). Moreover, BM MCD correlated positively with sRANKL, OPN and MIP-1 alpha (p<0.0001 for all cases), and negatively with OPG (r= -0.279 p<0.03). Conclusion: MCs are increased in MM BM and participate in many aspects of the disease. They may release various cytokines increasing myeloma growth and also may participate in the skeletal disease of MM rendering them as potential targets for therapy.

Bone disease mast cells multiple myeloma osteolysis

References (40)

  1. 1 Osteoclast differentiation and activation [DOI]
  2. 2 Osteoprotegerin Ligand Is a Cytokine that Regulates Osteoclast Differentiation and Activation [DOI]
  3. 3 International Staging System for Multiple Myeloma [DOI]
  4. 4 Chemokines and disease [DOI]
  5. 5 Understanding multiple myeloma pathogenesis in the bone marrow to identify new therapeutic targets [DOI]
  6. 6 Novel Antiangiogenic Effects of the Bisphosphonate Compound Zoledronic Acid [DOI]
  7. 7 RANK Is the Essential Signaling Receptor for Osteoclast Differentiation Factor in Osteoclastogenesis [DOI]
  8. 8 A randomized phase 2 study of lenalidomide therapy for patients with relapsed or relapsed and refractory multiple myeloma [DOI]
  9. 9 Mast Cells, Mastocytosis, and Related Disorders [DOI]
  10. 10 Macrophage inflammatory protein-1α is an osteoclastogenic factor in myeloma that is independent of receptor activator of nuclear factor κB ligand [DOI]
  11. 11 Accumulation of intraepithelial mast cells with a unique protease phenotype in TH2-high asthma [DOI]
  12. 12 Bortezomib Mediates Antiangiogenesis in Multiple Myeloma via Direct and Indirect Effects on Endothelial Cells [DOI]
  13. 13 Mast Cells as Sensors of Cell Injury through IL-33 Recognition [DOI]
  14. 14 Current treatment options in patients with mastocytosis: status in 2015 and future perspectives [DOI]
  15. 15 Human mast cell heterogeneity: Histamine release from mast cells dispersed from skin, lung, adenoids, tonsils, and colon in response to IgE-dependent and nonimmunologic stimuli [DOI]
  16. 16 Bone marrow angiogenesis and mast cell density increase simultaneously with progression of human multiple myeloma [DOI]
  17. 17 The oral combination of thalidomide, cyclophosphamide and dexamethasone (ThaCyDex) is effective in relapsed/refractory multiple myeloma [DOI]
  18. 18 Osteopontin: a bridge between bone and blood [DOI]
  19. 19 Mast cell contribution to angiogenesis related to tumour progression [DOI]
  20. 20 The Role of Mast Cell Specific Chymases and Tryptases in Tumor Angiogenesis [DOI]
  21. 21 Tumour angiogenesis and mast cell density in the prognostic assessment of colorectal carcinomas [DOI]
  22. 22 Osteopontin is produced by mast cells and affects IgE‐mediated degranulation and migration of mast cells [DOI]
  23. 23 The use of biochemical markers of bone remodeling in multiple myeloma: a report of the International Myeloma Working Group [DOI]
  24. 24 Macrophage inflammatory protein-1 alpha (LD78) expressed in human bone marrow: its role in regulation of hematopoiesis and osteoclast recruitment.
  25. 25 Bone marrow angiogenesis and progression in multiple myeloma.
  26. 26 Bortezomib as an Antitumor Agent [DOI]
  27. 27 Zoledronic acid affects over-angiogenic phenotype of endothelial cells in patients with multiple myeloma [DOI]
  28. 28 Mast Cells Contribute to Vasculogenic Mimicry in Multiple Myeloma [DOI]
  29. 29 Dynamic interplay between bone and multiple myeloma: Emerging roles of the osteoblast [DOI]
  30. 30 The osteoblastic niche in the context of multiple myeloma [DOI]
  31. 31 The antitumor potential of bisphosphonates [DOI]
  32. 32 CCR1 as a target for multiple myeloma [DOI]
  33. 33 Treatment strategies for bone disease [DOI]
  34. 34 Circulating osteopontin: a dual marker of bone destruction and angiogenesis in patients with multiple myeloma [DOI]
  35. 35 Multiple myeloma: a clinical overview.
  36. 36 Positive correlation between bone marrow mast cell density and ISS prognostic index in patients with multiple myeloma [DOI]
  37. 37 Novel Therapeutic Approaches Targeting Vascular Endothelial Growth Factor and its Receptors in Haematological Malignancies [DOI]
  38. 38 Osteopontin as a new player in mast cell biology [DOI]
  39. 39 The Impact of Mast Cell Density on the Progression of Bone Disease in Multiple Myeloma Patients [DOI]
  40. 40 Mast Cells Influence the Proliferation Rate of Myeloma Plasma Cells [DOI]

Cited by 0

No indexed citations yet.

Article metrics

Real usage data collected on this platform.

20

Page views

0

PDF downloads

0

Outbound clicks

0

Citations

Views over time

Views by country

Approximate, from request IP at view time — not citizenship or institution. Countries with fewer than 5 views are grouped as "Other".

Traffic sources

Referring site, by host.

Views and downloads exclude known bots/crawlers. Citations combines this platform's own DOI-resolved index with each external source's own reported total — see Cited by above for individually listed citing works. Last refreshed 0 seconds ago.