Short Communication: Expression of Apoptosis Regulating Factors on T Lymphocytes in Multiple Myeloma Patients.

Multiple myeloma (MM) is a malignant proliferation of plasma cells in which dysregulation of programmed cell death (apoptosis) is responsible for tumor cell expansion. However some phenotypic and functional alterations of T cells in MM patients have been reported, that also can influence the plasma cell growth. The aim of the study was to assess some aspects of T lymphocyte apoptosis in MM to obtain a better understanding of the changes in the immune system in this disease. Flow cytometry was used to analyze the expression of two main regulators of apoptosis: the pro-apoptotic Fas antigen and the anti-apoptotic protein BCL-2 in patients with untreated MM and in healthy controls. ELISA was used to determine soluble Fas ligand (sFasL) serum levels in patients and control groups. We detected statistically significant higher Fas expression in patients than in controls both on CD4 and CD8 lymphocytes, but no differences in BCL-2 expression by these cells. The sFasL level was statistically significant lower in patients than in controls. Our results indicate that T cells in MM are controlled by up-regulation of Fas. The Fas/FasL system induces the killing of T cells expressing Fas antigen, what could account for the incapability of the immune system to protect host against tumor expansion.

Assessment of Apoptosis Regulating Factors BCL-2 and Fas Antigens on Malignant and Normal Plasma Cells.

Multiple myeloma (MM) is characterised by slow proliferation of malignant plasma cells and their accumulation within the bone marrow. The dysregulation of programmed cell death (apoptosis) is a very important mechanism in the pathogenesis of this tumour. It prompted us to investigate the apoptosis regulating factors such as the pro-apoptotic Fas antigen and the anti-apoptotic protein BCL-2 on bone marrow malignant plasma cells in untreated patients with newly diagnosed MM and to compare them with their normal counterparts-plasma cells isolated from bone marrow of healthy individuals. Twenty-nine MM patients and 16 healthy persons were studied. Bone marrow mononuclear cells were isolated, indicated by monoclonal antibodies and analysed using the flow cytometry method. There was no statistically significant difference in BCL-2 expression in plasma cells between patients and control groups. However the percentage of BCL-2 positive cells was significantly related to the clinical stage of the disease. We detected statistically significant lower percentage of Fas positive cells in the patient group than in control. We concluded that in MM at diagnosis the expression of BCL-2 in bone marrow malignant plasma cells was comparable to normal plasma cells but expression of Fas antigen on these cells was lower. It suggests that down regulation of Fas and normal regulation of BCL-2 may be implicated for myeloma cell survival and their escape from apoptosis in vivo.