Moreover, non-mutational NOTCH1 activation found in ~50% of CLL cells lacking a NOTCH1 mutation implies that even an extended panel including SPEN, SF3B1, FBXW7 and MED12 mutations will neither be sufficient to identify all patients with abnormally strong NOTCH1 signalling. This evidence concerns the gene MED12 and B-cell chronic lymphocytic leukemia.