The Role of Activated NOTCH Signaling in Childhood T-ALL

We aimed to define novel molecular risk markers in T-ALL. In a first step, we analyzed activating Notch pathway mutations in >300 patients of the pediatric ALL-BFM 2000 study. Activating mutations of the NOTCH1 receptor and inactivating mutations of the NOTCH inactivator FBXW7 are associated with excellent early treatment response and long-term outcome. A detailed comparison with other studies suggested that the intensity of CNS-directed treatment might play a particularly important role in NOTCH activated patients. This interpretation is supported by the finding of the chemokine receptor CCR7 being a NOTCH targ…