The combination of PF-03084014 with fludarabine had a synergic antileukemic effect in primary Notch-1-mutated CLL cells, even in the presence of protective stroma, which was mediated through upregulation of proapoptotic HRK, downregulation of MMP9, IL32, RAC2 related to invasion and chemotaxis, and overcoming fludarabine-induced activation of NF-κB signaling [590]. The gene discussed is NOTCH1; the disease is B-cell chronic lymphocytic leukemia.