Proposed model of NICD degradation in CLL patients with and without FBXW7 mutations. NICD is targeted by wt FBXW7 (A), whereas mutations in the FBXW7 substrate binding domain G423V and W425C result in insufficient recognition of NICD (B; triangles). In contrast, mutations A503V as well as α-specific mutations T15VR and V154I do not impact on NICD binding (B; circle).