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

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.