FBXW7 is a ubiquitin protein ligase subunit which regulates levels of NOTCH, cyclin E, and other proteins. Loss-of-function mutations of FBXW7 lead to constitutive Notch1 pathway activation via inhibition of ubiquitin-mediated degradation of activated NOTCH1 and MYC. Mutations of FBXW7 include missense and frameshift mutations. FBXW7 have been reported in approximately 4-30% of cases of T-ALL less than 5% of cases of B-ALL, less than 5% of cases of CLL and appear to be very rare/absent in acute myeloid leukemia. According to some, but not all studies, NOTCH1 pathway activation by NOTCH1 mutations or FBXW7 mutations in TALL have been associated with an improved prognosis (in cases without concomitant RAS or PTEN mutations) compared to cases without mutations in NOTCH1 or FBXW7. FBXW7 mutations may occur alone or together with mutations in NOTCH1 (typically those in the heterodimerization domain and more rarely those in the PEST domain of NOTCH1). FBXW7 mutations may result in resistance to gamma secretase inhibitors according to some experimental studies.