WNT3 and LEF1 as markers for diagnosis and survival prediction in chronic lymphocytic leukemia patients

Background The Wnt pathway is aberrantly activated in chronic lymphocytic leukemia (CLL) and contributes to the antiapoptotic and mitogenic characteristics of CLL cells. Lymphoid enhancer-binding factor-1 (LEF1) acts as a mediator and key transcription factor of the Wnt/beta-catenin pathway. LEF1 helps to regulate important genes involved in tumor cell death mechanisms. Objective To analyze the expression levels of Wnt signaling pathway member (WNT3) and its key mediator LEF1 in Egyptian CLL patients and to detect the potential use of these genes as markers of CLL outcome. Methods We quantified the expression levels of Wnt3 and LEF1 in peripheral blood mononuclear cells of 30 untreated CLL and 19 healthy controls by qRT-PCR (quantitative real time polymerase chain reaction). Results Our study demonstrated significant upregulation of both Wnt3 and LEF1 in CLL (P< 0.0001). WNT3 and LEF1 were significantly decreased in CLL patients with ECOG performance 2 and 3 than those with 0 and 1 (p= 0.023 and 0.007, respectively). CLL patients with 17p deletion express significantly low LEF1 (p= 0.033). Low levels of WNT3 and LEF1 expression indicated a shorter overall survival (P= 0.007, 0.005, respectively). The predictive power of WNT3 and LEF1 expression showed good discrimination of CLL patients from controls (AUC >0.9). Conclusion Upregulation of WNT3 and LEF1 could be used as helpful and specific markers to distinguish our CLL patients. Low WNT3 and LEF1 expression is associated with shortened survival in CLL patients. These results indicate that WNT3 and LEF1 represent an attractive therapeutic target for future therapies in Egyptian CLL patients.