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. The gene discussed is SF3B1; the disease is B-cell chronic lymphocytic leukemia.