In this context, mutations in the heterodimer and PEST domains of Notch1, which confer ligand-independent cleavage of Notch1 and resistance to CDK8/FBXW7-mediated phosphorylation and degradation of NICD1, have been frequently identified in patients with acute T cell lymphoblastic leukemia (T-ALL)25,26. The gene discussed is NOTCH1; the disease is T-cell acute lymphoblastic leukemia.