Contributions
Abstract: PB1961
Type: Publication Only
Background
Multiple myeloma (MM) is a malignant proliferation of plasma cells and is characterized by the accumulation of monoclonal plasma cells in bone marrow that secrete pathological monoclonal immunoglobulins. Inductive factors secreted by tumor cells and other cells of the marrow microenvironment play an important role in disease progression. APRIL, by initial letters A Proliferation Inducing Ligand, is a member of the family of pro TNF, one of the main factors for the survival of immature and activated B cells. One of the main signal transduction pathways for activation of myeloma cells is NF-κB. APRIL, can directly activate the NF -κB and has been found by studies that are the most important factors for the survival of healthy and myeloma cells.
Aims
Aim of this study was the study of APRIL expression in myeloma cells in the bone marrow of patients with MM and their possible association with cell proliferation markers.
Methods
We studied 42 newly diagnosed patients with MM, 19 women and 23 men, aged 64,1 ± 10,4 years. According to the ISS stage, 14 were stage I, 11 stage II and 17 stage III . Regarding the type of paraprotein that had been found, 23 IgG, 14 IGA and 5 patients with light chains. 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. 20 age and sex-matched healthy volunteers, were used as controls. The levels of IL-10 and IL-6 in the serum were measured by ELIZA. Bone marrow infiltration by neoplastic plasma cells was calculated in %.
The expression of cell proliferation index was calculated in BM biopsy sections with immunohistochemistry techniques. The expression of APRIL was also calculated with immunohistochemistry. For the control of the process we used positive control. The assessing of the staining was checked in the optical microscope, over the whole surface of each sample and had to do with the cytoplasm of tumor cells. It was dotted with brown ting. Non-specific staining was observed at the other cellular components of BM. The degree of staining expression was evaluated as the percentage of neoplastic plasma cells and according to the intensity of staining in four-grade scale 0: negative, + 1 weak, +2 moderate and +3 intense staining. Then the proportion of plasma cells stained for each type of staining separately, was calculated using the H-score method (Histoscore), based on the formula:% *% * 1 + 2 + 3% *. Our aim is to prove if the intensity of expression is associated with disease stage.
Results
Statistically significant differences were observed between patients and controls for all parameters measured (p <0.001 in all cases) . All values of the measured parameters increased in parallel with the ISS stages of the disease (APRIL p <0,005, bone marrow infiltration p <0.03 Ki-67p <0,01, IL-10 p <0,001, IL-6, p < 0.001) Eventually APRIL correlated significantly with all measured parameters e.g. BM infiltration r = 0,386, p <0,01, with Ki-67 r = 0,390 p <0,01 IL-10 r = 0,497 p <0,001, IL-6, r = 0,484 p <0,001)
Conclusion
Increased expression of APRIL ligand plays an important role in development and pathobiology of MM and may be an important therapeutic target in the treatment of MM.
Session topic: 14. Myeloma and other monoclonal gammopathies - Clinical
Keyword(s): Proliferation, Multiple Myeloma
Abstract: PB1961
Type: Publication Only
Background
Multiple myeloma (MM) is a malignant proliferation of plasma cells and is characterized by the accumulation of monoclonal plasma cells in bone marrow that secrete pathological monoclonal immunoglobulins. Inductive factors secreted by tumor cells and other cells of the marrow microenvironment play an important role in disease progression. APRIL, by initial letters A Proliferation Inducing Ligand, is a member of the family of pro TNF, one of the main factors for the survival of immature and activated B cells. One of the main signal transduction pathways for activation of myeloma cells is NF-κB. APRIL, can directly activate the NF -κB and has been found by studies that are the most important factors for the survival of healthy and myeloma cells.
Aims
Aim of this study was the study of APRIL expression in myeloma cells in the bone marrow of patients with MM and their possible association with cell proliferation markers.
Methods
We studied 42 newly diagnosed patients with MM, 19 women and 23 men, aged 64,1 ± 10,4 years. According to the ISS stage, 14 were stage I, 11 stage II and 17 stage III . Regarding the type of paraprotein that had been found, 23 IgG, 14 IGA and 5 patients with light chains. 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. 20 age and sex-matched healthy volunteers, were used as controls. The levels of IL-10 and IL-6 in the serum were measured by ELIZA. Bone marrow infiltration by neoplastic plasma cells was calculated in %.
The expression of cell proliferation index was calculated in BM biopsy sections with immunohistochemistry techniques. The expression of APRIL was also calculated with immunohistochemistry. For the control of the process we used positive control. The assessing of the staining was checked in the optical microscope, over the whole surface of each sample and had to do with the cytoplasm of tumor cells. It was dotted with brown ting. Non-specific staining was observed at the other cellular components of BM. The degree of staining expression was evaluated as the percentage of neoplastic plasma cells and according to the intensity of staining in four-grade scale 0: negative, + 1 weak, +2 moderate and +3 intense staining. Then the proportion of plasma cells stained for each type of staining separately, was calculated using the H-score method (Histoscore), based on the formula:% *% * 1 + 2 + 3% *. Our aim is to prove if the intensity of expression is associated with disease stage.
Results
Statistically significant differences were observed between patients and controls for all parameters measured (p <0.001 in all cases) . All values of the measured parameters increased in parallel with the ISS stages of the disease (APRIL p <0,005, bone marrow infiltration p <0.03 Ki-67p <0,01, IL-10 p <0,001, IL-6, p < 0.001) Eventually APRIL correlated significantly with all measured parameters e.g. BM infiltration r = 0,386, p <0,01, with Ki-67 r = 0,390 p <0,01 IL-10 r = 0,497 p <0,001, IL-6, r = 0,484 p <0,001)
Conclusion
Increased expression of APRIL ligand plays an important role in development and pathobiology of MM and may be an important therapeutic target in the treatment of MM.
Session topic: 14. Myeloma and other monoclonal gammopathies - Clinical
Keyword(s): Proliferation, Multiple Myeloma