– Notch activating mutation are observed in CLL patients (Willander et al., 2013). – Notch1 mutation is found in intermediate-risk patients, predicting poorer survival (Willander et al., 2013). – Higher expression and activation of Notch signaling is observed in refractory patients (Rosati et al., 2013). – Wnt5 is enriched in CLL patients (Janovska et al., 2016). – Low WNT3 expression is a signature of patient with short therapy-free survival (Janovská and Bryja, 2017). This evidence concerns the gene NOTCH1 and B-cell chronic lymphocytic leukemia.