Contributions
Abstract: PB1950
Type: Publication Only
Background
Angiogenesis in the bone marrow plays a very important role in the progression of multiple myeloma(MM). The procedure of angiogenesis is supported by several factors such as VEGF, FGF-2 and metalloproteases that are secreted straight from the tumor cells. The presence of IL-6 in the microenvironment, induces the production and the secretion of several angiogenic factors that activate inflammatory cells of the matrix, like macrophages and mast cells to secrete more angiogenic factors. IL-17 is among the most important cytokines that have an important role in the development of myeloma tumor. IL-17 is a proinflammatory cytokine that is secreted primarily by CD4 (activated memory cells) and stimulate macrophages, fibroblasts and other cells that release several cytokines. It has been reported that IL-17, induces angiogenesis in humans by stimulating the migration of vessel endothelial cells and adjusting the production of various proangiogenic factors. In a previous study, it was found that increased levels in stage II and stage III, resolved after therapy. Additionally, blocking the receptor of IL-17, with an antibody, cancels the effects of IL-17.
Aims
Aim of this study is to assess the relationship of the MCD and IL-17, in angiogenesis of MM, as well as their correlation with known angiogenic factors in disease progression
Methods
We studied 52 newly diagnosed patients with MM, 32 women and 20 men, aged 67,5 ± 9,6 years. According to the ISS stage, 19 were stage I, 17 stage II and 16 stage III . Regarding the type of paraprotein that had been found, 31 IgG, 17 IgA and 4 patients with light chains. 20 age and sex-matched healthy volunteers, were used as controls. Serum samples and bone marrow biopsy samples were obtained from all patients prior to the initiation of treatment. Patients with impaired hepatic and renal function, chronic or acute infections, chronic inflammatory or autoimmune disorders or other malignancies were excluded from the study.We also excluded patients who were taking anti-inflammatory drugs, corticosteroids or bisphosphonates. IL-17, bFGF and ANGIOP-2 were measured in patients’ serum with ELISA method according to the manufacturer’s instructions. The MCD assessed after immunohistochemical staining using monoclonal antibody to mast cell tryptase. The MCD was measured in three hot spots (maximum vasculature area) x 100 and then we measured mast cells x 400, using a graduated slide which corresponds to an area of 0.0625 mm2 . MCD was calculated as mean MCD / HPF.
Results
Statistically significant differences between patients and controls were observed in all measured parameters, MCD (p <0.001), bFGF (p <0.01) and ANGIOP-2 (p <0.01), and for IL-17 (p <0.04). All parameters were increased in parallel with ISS stages (p <0.001) in all cases. Finally, the MCD and IL-17 correlated significantly with all the measured parameters (p <0.001)
Conclusion
The mast cells increase in the bone marrow(BM) of patients with MM. They release several transmitters that promote directly and indirectly the development of disease progress of MM also accompanied by increased angiogenesis in BM. In conclusion, mast cells and angiogenic factors seem to be important elements in the development of MM and become potential targets for the treatment and prognosis of the disease.
Session topic: 14. Myeloma and other monoclonal gammopathies - Clinical
Keyword(s): Multiple Myeloma, Mast cell, Angiogenesis
Abstract: PB1950
Type: Publication Only
Background
Angiogenesis in the bone marrow plays a very important role in the progression of multiple myeloma(MM). The procedure of angiogenesis is supported by several factors such as VEGF, FGF-2 and metalloproteases that are secreted straight from the tumor cells. The presence of IL-6 in the microenvironment, induces the production and the secretion of several angiogenic factors that activate inflammatory cells of the matrix, like macrophages and mast cells to secrete more angiogenic factors. IL-17 is among the most important cytokines that have an important role in the development of myeloma tumor. IL-17 is a proinflammatory cytokine that is secreted primarily by CD4 (activated memory cells) and stimulate macrophages, fibroblasts and other cells that release several cytokines. It has been reported that IL-17, induces angiogenesis in humans by stimulating the migration of vessel endothelial cells and adjusting the production of various proangiogenic factors. In a previous study, it was found that increased levels in stage II and stage III, resolved after therapy. Additionally, blocking the receptor of IL-17, with an antibody, cancels the effects of IL-17.
Aims
Aim of this study is to assess the relationship of the MCD and IL-17, in angiogenesis of MM, as well as their correlation with known angiogenic factors in disease progression
Methods
We studied 52 newly diagnosed patients with MM, 32 women and 20 men, aged 67,5 ± 9,6 years. According to the ISS stage, 19 were stage I, 17 stage II and 16 stage III . Regarding the type of paraprotein that had been found, 31 IgG, 17 IgA and 4 patients with light chains. 20 age and sex-matched healthy volunteers, were used as controls. Serum samples and bone marrow biopsy samples were obtained from all patients prior to the initiation of treatment. Patients with impaired hepatic and renal function, chronic or acute infections, chronic inflammatory or autoimmune disorders or other malignancies were excluded from the study.We also excluded patients who were taking anti-inflammatory drugs, corticosteroids or bisphosphonates. IL-17, bFGF and ANGIOP-2 were measured in patients’ serum with ELISA method according to the manufacturer’s instructions. The MCD assessed after immunohistochemical staining using monoclonal antibody to mast cell tryptase. The MCD was measured in three hot spots (maximum vasculature area) x 100 and then we measured mast cells x 400, using a graduated slide which corresponds to an area of 0.0625 mm2 . MCD was calculated as mean MCD / HPF.
Results
Statistically significant differences between patients and controls were observed in all measured parameters, MCD (p <0.001), bFGF (p <0.01) and ANGIOP-2 (p <0.01), and for IL-17 (p <0.04). All parameters were increased in parallel with ISS stages (p <0.001) in all cases. Finally, the MCD and IL-17 correlated significantly with all the measured parameters (p <0.001)
Conclusion
The mast cells increase in the bone marrow(BM) of patients with MM. They release several transmitters that promote directly and indirectly the development of disease progress of MM also accompanied by increased angiogenesis in BM. In conclusion, mast cells and angiogenic factors seem to be important elements in the development of MM and become potential targets for the treatment and prognosis of the disease.
Session topic: 14. Myeloma and other monoclonal gammopathies - Clinical
Keyword(s): Multiple Myeloma, Mast cell, Angiogenesis