T-ALL is one of the most aggressive leukemias and has a poor prognosis.6–11 A tremendous amount of research has focused on the oncogenic mechanisms by which NOTCH1 enhances leukemogenesis via downstream genes or interaction with other important signaling pathways, such as NF-κB and PI3K-AKT-mTOR pathways.12,13 However, the upstream mechanisms sustaining aberrant NOTCH1 signaling activities are incompletely understood, especially NOTCH1 protein turnover. The gene discussed is NOTCH1; the disease is leukemia.