Notch1 activation and inhibition in T-cell acute lymphoblastic leukemia subtypes

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignancy caused by the accumulation of genomic lesions that affect the development of T cells. Notch1 signaling controls the expression of numerous T-lineage genes, thus playing essential parts in T-cell differentiation. T-ALL can be classified into two subtypes according to the immunophenotypic and genetic makeup: early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) and non-ETP-ALL. The relationship between constitutive activation of Notch1 signaling and non-ETP-ALL has been thoroughly studied; however, how Notch1 signaling influences ETP-ALL remains unclear. Targeting Notch1 signaling is a promising treatment for T-ALL, and γ-secretase inhibitors (GSIs), which prevent Notch1 signaling from being activated, show a degree of antineoplastic activity in previous clinical development. But these agents just have satisfactory effects in non-ETP-ALL; further study should be carried out to investigate fitting targeting drugs.