PEST-domain NOTCH1 mutations therefore should reinforce pro-survival signals after rituximab treatment due to their activating effect on NICD1 potentially explaining the reduced benefit of adding rituximab to chemotherapy in NOTCH1 mutant CLL (Stilgenbauer et al., 2014; Weng et al., 2004). This evidence concerns the gene NOTCH1 and B-cell chronic lymphocytic leukemia.