Notch in T-ALL: new players in a complex disease

T cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematopoietic malignancy of thymocytes affecting preferentially children and adolescents. The disease is heterogeneous and characterized by a large set of chromosomal and genetic alterations that deregulate the growth of maturing thymocytes. The identification of activating point mutations in NOTCH1 in more then 50% of all T-ALL cases highlights the NOTCH1 cascade as a central player of T-ALL pathogenesis. In this review, we summarize and update more recent findings on the molecular mechanisms of T-ALL with a particular emphasis on the oncogenic properties of aberrant NOTCH1 signaling.