In wild-type NOTCH1 CLL cells, NOTCH intracellular domain (NICD) controls promoter methylation of the dual specificity protein phosphatase 22 (DUSP22) tumor suppressor gene that encodes a phosphatase that inactivates MAPKs, including c-jun N-term kinase (JNK) and p38, and dephosphorylates STAT3 (65). The gene discussed is DUSP22; the disease is B-cell chronic lymphocytic leukemia.