By quantifying two disease endpoints, T-ALL penetrance and disease latency, i.e. the median time to overt leukemia, we show that in the context of the SCL and LMO1 oncogenes, the hyperactive Notch1 oncogene on its own determines disease penetrance even in the absence of pre-TCR signaling. This evidence concerns the gene TAL1 and acute lymphoblastic leukemia.