Abnormal Notch signaling accelerates the proliferation of CLL cells and contributes to disease progression.180,181 In B-cell CLL cells, the oncogenic gene Notch2 is highly expressed and associated with disease-specific apoptosis failure.182 Notch2 high expression characterizes a subset of patients with CLL, mainly carrying trisomy 12, which is marked by high levels of Mcl-1.183 Silencing Notch2 to reduce Mcl-1 expression can restore the response of CLL cells to venetoclax treatment. The gene discussed is MCL1; the disease is B-cell chronic lymphocytic leukemia.