Association of GRP78, HIF-1α and BAG3 Expression with the Severity of Chronic Lymphocytic Leukemia

Introduction: Parallel with the progression of Chronic Lymphocytic Leukemia (CLL), the levels of 78KDa Glucose-Regulated Protein (GRP78) and Hypoxia-Inducible Factor 1 alpha (HIF-1 alpha) are increased as they may activate the induction of anti-apoptotic proteins such as BCL2 Associated Athanogene 3 (BAG3). Previous studies have indicated that there is a positive correlation among GRP78, HIF-1 alpha and BAG3. Objective: This study aimed to evaluate the effect of metabolic factors involved in invasive CLL on apoptotic factors. Methods: A case-control study was conducted on 77 patients diagnosed with CLL along with 100 healthy individuals. Cell blood count was performed for all participants. According to Binet's classification, CLL patients were divided into different groups. B cells were isolated from the peripheral blood of CLL patients by binding to anti-CD19 beads. The expression of BAG3, GRP78 and HIF-1 alpha genes was analyzed using the RT-PCR method. To confirm the results of RT-PCR, western blot analysis was carried out. Results: The results showed that there was a strong association among the expression of BAG3, GRP78 and HIF-1 alpha. The stage of CLL in patients was highly correlated with the expression rate of each gene (p<0.001). Accordingly, the western blot analysis indicated that the concentrations of GRP78 and HIF-1 alpha were significantly higher than the expression of BAG3, considering the stage of CLL. Conclusion: It was shown that increased expression of GRP78 and HIF-1 alpha could result in the elevation of BAG3, as well as the disease progression. Therefore, the role of these metabolic factors might be more pronounced compared with the anti-apoptotic agents to monitor disease progression in CLL patients.