Soon after NOTCH1 mutations were identified in CLL, several retrospective analyses demonstrated that NOTCH1-mutated patients have inferior survival and worse treatment outcomes compared with NOTCH1 wild-type patients [11,14,15,165,166,167,168,169,170], albeit with discordant results regarding the impact on overall survival or progression-free survival [16,170,171,172]. This evidence concerns the gene NOTCH1 and B-cell chronic lymphocytic leukemia.