NOTCH1 and B-cell chronic lymphocytic leukemia: In this context, we demonstrated that, in NOTCH1-mutated CLL, the loss of the PEST domain altered the phosphorylation status of mutated NOTCH1 protein and generated a phosphorylated NOTCH1-ICD form that accumulated in the nucleus, leading to increased NOTCH1 signaling and prolonged CLL cell survival (153).