In animal models, irinotecan, a clinical Topo1 inhibitor, eradicated activated-Notch1 (Notch1-ΔE-IRES-GFP) driven AtmKD/- T cell leukemia, but not the isogenic parental AtmKD/C leukemia in vivo, determined by the absence of GFP+ leukemia cells in the spleen, reduced spleen size and weight, lack of infiltrated leukemia blasts and increased TUNEL+ apoptotic cells (Figure 4A–F and Figure 4—figure supplement 1A–B). Here, NOTCH1 is linked to leukemia.