Conversely, a role in sustaining the levels of N1-ICD is played by IL-4-induced PI3Kδ/AKT pathway [19] and BCR-induced BTK [20, 21], suggesting that crosstalk among multiple deregulated signaling molecules controls NOTCH1 activation in CLL. The gene discussed is NOTCH1; the disease is B-cell chronic lymphocytic leukemia.