Assessment of Apoptosis Regulating Factors BCL-2 and Fas Antigens on Malignant and Normal Plasma Cells
A Dmoszynska1, M Podhorecka2, A Khmaj1
1a Department of Haematology , University School of Medicine , Jaczewskiego 8, 20-950 , Lublin , Poland.
Abstract:
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.
Insights
In newly diagnosed multiple myeloma (MM), malignant plasma cells show lower Fas antigen expression but normal BCL-2 levels compared to healthy individuals. This suggests Fas downregulation contributes to myeloma cell survival and resistance to apoptosis.
Area of Science:
- Oncology
- Immunology
- Cell Biology
Background:
- Multiple myeloma (MM) is a hematologic malignancy characterized by malignant plasma cell proliferation in the bone marrow.
- Dysregulation of programmed cell death (apoptosis) is a key factor in MM pathogenesis.
- Investigating apoptosis regulators like Fas and BCL-2 in MM is crucial.
Purpose of the Study:
- To compare the expression of pro-apoptotic Fas antigen and anti-apoptotic BCL-2 protein on malignant plasma cells in newly diagnosed MM patients versus normal plasma cells.
- To assess the relationship between BCL-2 expression and clinical stage in MM patients.
Main Methods:
- Bone marrow mononuclear cells were isolated from 29 MM patients and 16 healthy individuals.
- Cells were analyzed using flow cytometry with monoclonal antibodies to identify plasma cells and quantify Fas and BCL-2 expression.
- Statistical analysis was performed to compare expression levels between groups and correlate with disease stage.
Main Results:
- No significant difference in BCL-2 expression was observed between MM patients and controls.
- BCL-2 expression in plasma cells showed a significant correlation with the clinical stage of MM.
- A statistically significant lower percentage of Fas-positive plasma cells was detected in MM patients compared to healthy controls.
Conclusions:
- In newly diagnosed MM, BCL-2 expression in malignant plasma cells is comparable to normal plasma cells.
- Downregulation of Fas antigen expression on malignant plasma cells suggests its role in myeloma cell survival.
- Normal BCL-2 regulation, coupled with Fas downregulation, may contribute to myeloma cell resistance to apoptosis in vivo.
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