The underlying mechanism is that free HDAC, displaced from the RBPJk-tethered complex by an excess of NICD, can interact with and stabilize DNMT3A, which in turn suppresses the expression of the tumor suppressor gene DUSP22. Loss of DUSP22 phosphatase activity leads to aberrant activation of MAPK and STAT3 signaling, both crucial in CLL homeostasis as downstream players of growth and chemokine receptors, and consequently to a STAT3-dependent upregulation of CCR7 expression and responsiveness (66). The gene discussed is STAT3; the disease is B-cell chronic lymphocytic leukemia.