F-box and WD40 repeat domain containing-7 (FBXW7), an E3 ubiquitin ligase, has been reported to recognize and bind to the Notch1 PEST domain, leading to degradation of the activated form of Notch1.164,165 FBXW7 mutations stabilize intracellular Notch1 in the nucleus and are thought to work synergistically with the Notch1 PEST mutations.166,167 An early study involving 141 adult T-ALL samples identified 62% with Notch1 mutations and 24% with FBXW7 mutations. The gene discussed is NOTCH1; the disease is acute lymphoblastic leukemia.