ABSTRACT
Objective: Multiple myeloma, which affects plasma cells, is the second most common hematological malignancy. Despite the development of new drugs and treatment protocols, patient survival has not reached the desired level. In this study, we investigated the effects of Myxoma virus (MYXV), an oncolytic virus, on autophagy in myeloma cells. Materials and Methods: We analyzed protein expressions of ATG-5, p62, Beclin-1, LC3B, and the apoptosis marker Bcl-2 as autophagy markers in human U-266 and mouse MOPC-315 myeloma cell lines subjected to different doses of MYXV. In addition, autophagic images of myeloma cells were investigated using transmission electron microscopy (TEM). Results: In the first 24 h, which is the early stage of autophagy, ATG-5 and Beclin-1 expression levels were increased in the U-266 and MOPC-315 cell lines in the groups that had received MYXV at a multiplicity of infection of 15. At 48 h, a significant increase was detected in the expression of LC3B, which is a late indicator. Autophagosomes were observed in myeloma cells by TEM. Conclusion: MYXV shows an antimyeloma effect by increasing autophagy in myeloma cells.
Subject(s)
Multiple Myeloma , Myxoma virus , Oncolytic Viruses , Animals , Mice , Humans , Multiple Myeloma/therapy , Multiple Myeloma/pathology , Myxoma virus/genetics , Beclin-1/genetics , Cell Line, Tumor , AutophagyABSTRACT
This study aimed to explore the effectiveness and safety of Myxoma virus (MYXV) in MM cell lines and primary myeloma cells obtained from patients with multiple myeloma. Myeloma cells were isolated from MM patients and cultured. MYXV, lenalidomide, and bortezomib were used in MM cells. The cytotoxicity assay was investigated using WST-1. Apoptosis was assessed through flow cytometry with Annexin V/PI staining and caspase-9 concentrations using ELISA. To explore MYXV entry into MM cells, monoclonal antibodies were used. Moreover, to explore the mechanisms of MYXV entry into MM cells, we examined the level of GFP-labeled MYXV within the cells after blocking with monoclonal antibodies targeting BCMA, CD20, CD28, CD33, CD38, CD56, CD86, CD117, CD138, CD200, and CD307 in MM cells. The study demonstrated the effects of treating Myxoma virus with lenalidomide and bortezomib. The treatment resulted in reduced cell viability and increased caspase-9 expression. Only low-dose CD86 blockade showed a significant difference in MYXV entry into MM cells. The virus caused an increase in the rate of apoptosis in the cells, regardless of whether it was administered alone or in combination with drugs. The groups with the presence of the virus showed higher rates of early apoptosis. The Virus, Virus + Bortezomib, and Virus + Lenalidomide groups had significantly higher rates of early apoptosis (p < 0.001). However, the measurements of late apoptosis and necrosis showed variability. The addition of MYXV resulted in a statistically significant increase in early apoptosis in both newly diagnosed and refractory MM patients. Our results highlight that patient-based therapy should also be considered for the effective management of MM.
ABSTRACT
BACKGROUND: We have aimed at exposing left ventricular diastolic functions and the presence of known genetic mutations for familial erythrocytosis, in patients who exhibit idiopathic erythrocytosis. METHODS: Sixty-four patients with idiopathic erythrocytosis (mean age, 46.4 ± 2.7 years) and 30 age-matched healthy subjects were prospectively evaluated. The regions of interest of the erythropoietin receptor, hemoglobin beta-globin, von Hippel-Lindau, hypoxia-inducible factor 2 alpha, and Egl-9 family hypoxia-inducible factor genes were amplified by PCR. Left ventricular (LV) mass was measured by M-mode and 2-dimensional echocardiography. LV diastolic functions were assessed by conventional echocardiography and tissue Doppler imaging. RESULTS: As a result of genetic analyses, genetic mutations for familial erythrocytosis were detected in 5 patients. It has been observed in our study that the risk of cardiovascular disorders is higher in patients. Interventricular septum thickness, left atrial diameter, and some diastolic function parameters such as deceleration time and isovolumetric relaxation time have been found to be significantly higher in idiopathic erythrocytosis group than in the controls. CONCLUSION: This study has shown that LV diastolic functions were impaired in patients with idiopathic erythrocytosis. In this patient group with increased risk of cardiovascular disorders, the frequent genetic mutations have been detected in 5 patients only. Therefore, further clinical investigations are needed as novel genetic mutations may be discovered in patients with idiopathic erythrocytosis because of cardiovascular risk.
