ABSTRACT
Venetoclax, a specific inhibitor of the BCL2 protein, is administered for the treatment of acute lymphoblastic leukemia. However, despite being utilized in conjunction with chemotherapy, the drug exhibits instances of resistance. The exact mechanisms responsible for this resistance remain relatively obscure. Within the context of this investigation, the study aimed to explore the involvement of anti- and pro-apoptotic proteins as one of the potential mechanisms underlying this resistance phenomenon. Blast cells were extracted from patients diagnosed with B&T acute lymphoid leukemia. Subsequently, these cells were subjected to a cultivation process. Following the cultivation, treatment with the Venetoclax drug was administered to both groups of B&T cells. Additionally, one group from each cell type was designated as a control. The relative expression levels of genes BCL-2, MCL-1, and BIM were assessed in comparison to the control group. Annexin V-fluorescein isothiocyanate and propidium iodide staining was done to check cell apoptosis. The results showed a significant increase in the expression of BIM gene and a significant decrease in BCL-2 gene compared to the control group, but the change in the expression of MCL-1 gene was not significant. Also, an increase in apoptosis was observed in the treatment groups compared to the control. Although it was shown that changes in the expression of pro- and anti-apoptotic genes can lead to an increase in cell apoptosis and a decrease in the number of blast cells, more studies are needed to investigate the simultaneous effect of Venetoclax drug with other drugs and also in the form of a clinical trial.
ABSTRACT
BACKGROUND: CD93 has originally been known as a C1q receptor, and many studies have demonstrated that CD93 is expressed on hematopoietic stem cells, B cell progenitors, myeloid and monocytic cells. Moreover, CD93 is shown to be expressed on long-lived plasma cells, and CD93 deficient-mice display an impairment in plasma cell development. OBJECTIVE: To investigate the expression of CD93 on multiple myeloma (MM) cells. METHODS: Human MM and B cell lines were cultured, and the expression of CD93 was examined on these cells by quantitative Reverse Transcription Polymerase Chain Reaction (qRT-PCR) and Fluorescence Activated Cell Sorting (FACS). In addition, CD19+ primary B cells and CD19-/CD138+ primary MM cells were isolated by MACS columns, and CD93 expression was further analyzed on these cells. RESULTS: qRT-PCR data showed that CD93 expression at mRNA level was much higher in MM cell lines compared with B cell lines. In addition, MM cell lines expressed a higher amount of surface CD93 at protein level compared with B cell lines. More importantly, CD93 expression was significantly higher in CD19-/CD138+ primary MM cells than in CD19+ primary B cells isolated from the bone marrow of patients with MM. CONCLUSION: We demonstrated that CD93 is expressed on myeloma cells and, that CD93 could play a key role in the pathogenesis of MM. Further studies are necessary to explore this possible role.
Subject(s)
B-Lymphocytes/immunology , Biomarkers, Tumor/metabolism , Bone Marrow/pathology , Membrane Glycoproteins/metabolism , Multiple Myeloma/immunology , Receptors, Complement/metabolism , Aged , Aged, 80 and over , Antigens, CD19/metabolism , Biomarkers, Tumor/genetics , Cell Differentiation , Cell Line, Tumor , Female , Gene Expression Regulation, Neoplastic , Humans , Male , Membrane Glycoproteins/genetics , Middle Aged , Multiple Myeloma/pathology , Receptors, Complement/geneticsABSTRACT
BACKGROUND: Hepatocyte Growth Factor (HGF) plays a pivotal role in hematopoiesis, motility, growth and mobilization of hematopoietic stem/progenitor cells (HSPCs). HGF mainly is produced by bone marrow mesenchymal stem cells (BM-MSCs). MSCs express erythropoietin (EPO) receptor. In this study, we aimed to assess the effect of EPO on HGF secretion in BM-MSCs. METHODS: The BM-MSCs treated with EPO (4 IU/ml) for 6, 24 and 48 h. HGF gene expression and protein level were assessed using quantitative real time PCR (qRT-PCR) and Enzyme-linked immunosorbant Assay. In order to show the effect of secreted HGF on migration of HSPCs, hematopoietic stem cells (HSCs) were isolated from cord blood and evaluated using transwell migration assay. RESULTS: We observed a significant increase in level of HGF in cell supernatant after 48 h compared to control group (P < 0.05). Also, qRT-PCR results demonstrated a significant elevation in HGF expression level after 24 and 48 h treatment with EPO compared to control group (P < 0.05). Finally, migration assay results showed a significant increase in migration of HSCs in treated group after 48 h. CONCLUSION: Our data indicated that EPO may play an important role in stem cell mobilization through up regulating HGF in MSCs and inducing migration of HSCs.
