NOTCH1 promotes T cell leukemia-initiating activity by RUNX-mediated regulation of PKC-θ and reactive oxygen species

The authors uncover a new mechanism for the regulation of the activity of leukemia-initiating cells in T-ALL. A subpopulation of stem cells with low amounts of reactive oxygen species (ROS) is enriched in their ability to reconstitute disease in mouse models, and this effect is regulated by repression of PKC-θ, which increases ROS production. Moreover, oncogenic NOTCH, a common T-ALL–driving alteration, regulates stem cell activity by increasing RUNX3 expression, which represses RUNX1, a PCK-θ activator, a pathway that is conserved in human patients.