T cell acute lymphoblastic leukemia (T-ALL) and lymphoma (T-LBL) are malignant diseases defined by a clonal expansion of cytoplasmic CD3 expressing T cell precursors with propensity to spread to the bone-marrow. According to the WHO criteria both diseases are only discriminated by a bone-marrow spreading equal to or more than 25% in T-ALL and less than 25% in T-LBL. Those malignancies are preferentially seen in male teenagers and young adults. T-ALL account for about 25% and about 15% of acute lymphoblastic leukemia in adult and children, respectively. T-LBL is an orphan disease in adult accounting for 1% to 2% of non-Hodgkin lymphomas and represent about 30% of non-Hodgkin lymphomas in pediatrics. A common feature to both diseases, in adult as well as in pediatrics, is an inferior outcome compared with their B cell counterpart. Moreover, again unlike their B cell counterpart relapses can rarely benefit from curative salvage treatment. Many cytogenetic abnormalities and several somatic variants in a variety of genes are described in T-ALL/T-LBL but none demonstrated a robust prediction of the outcome. Thus, until a recent period prognostic factors enable to discriminate patients for the best initial treatment intensity are missing. However, in the last 10 years constitutive activation of Notch1 pathway, a pathway of major importance in T cell commitment, was described in more than 50% of T-ALL raising the hypothesis of its prognostic impact in those diseases.

We present here some works illustrating our contribution to these discoveries, describing further the incidence of Notch1 activation pathway in T-ALL and in T-LBL and demonstrating the prognostic impact of Notch1 pathway in those malignancies. We also show some approaches to assess the opportunity to target Notch1 pathway in the treatment of acute T cell malignancies. Finally, we present the possibilities according to our works to implement Notch1 pathway activation in the current therapeutic approach of acute T cell lymphoblastic malignancies and further perspectives on characterization of other oncogenic pathways involved in those malignant hemopathies.