Can ELABELA be a Novel Target in the Treatment of Chronic Lymphocytic Leukaemia?

Abstract

Background: It has been shown that bcl2, bcl-XL and mcl-1 protein levels are high in chronic lymphocytic leukemia cells, and resultantly, apoptosis does not occur chronic lymphocytic leukemia cells. Apelin and apela (ELABELA/ELA/Toddler) are two peptide ligands for a class A G-protein coupled receptor called apelin receptor. Studies have shown that ELA inhibits apoptosis by inhibiting apoptotic proteins and activating anti-apoptotic proteins. Proteins and genes involved in apoptosis are valuable for targeted cancer therapy. We hypothesized that serum levels may be increased in patients with chronic lymphocytic leukemia based on the antiapoptotic effect of ELA. We compared serum apelin levels of healthy volunteers and patients with chronic lymphocytic leukemia. We aimed to draw attention to a new molecule worthy of research in targeted cancer treatment. Methods: 42 untreated CLL patients and 41 healthy volunteers were included in the study. Serum ELA levels were measured by using enzyme-linked immunosorbent assay kits (Dhanghai Sunred Biological Technology co. Ltd), automated ELISA reader (Thermo Scientific, FİNLAND) and computer program (Scanlt for Multiscan F.C.2.5.1) in accordance with the manufacturer’s instructions. Statistical analysis was done by Statistical Package for Social Sciences for Windows 20 (IBM SPSS Inc., Chicago, IL) ve MedCalc programs. ELA and variables related to CLL were correlated with Spearman correlation anlysis test. ROC analysis and Youden index method were used to determine a cut off point for ELA. All p-values were 2-sided with statistical significance at 0.05 alpha levels. Results: In our study, we found that serum ELA levels were significantly higher in patients with CLL. Conclusions: This study highlights that ELA targeting may be a potential therapeutic option for treating CLL. Keywords: ELABELA; apelinergic system; chronic lymphocytic leukaemia; apoptosis

Expression of the apelinergic system and its influence on functional properties of tumor cells

“…Chronic lymphocytic leukemia (Acik et al 2019) Elevated Apela (endogenous APJ agonist) may may potentiate progress of chronic lymphocytic leukemia.…”

“…It was recently demonstrated that blood levels of Apela (together with Apelin, endogenous agonist for the APJ receptor), were elevated in individuals with chronic lymphocytic leukemia (CLL) (Acik et al 2019). Accordingly, it was anticipated that a similar situation may occur in acute myeloid leukemia (after APJ overexpression), and a thorough screening of AML cell lines was carried out (Figure 3).…”