First, using an in vitro OP9/OP9-DLL1 co-culture system, we confirmed that T-ALL cases characterized by Notch1 PEST-domain mutations (T-ALL4, T-ALL13) required an exogenous source of Notch1 ligands for growth, whereas T-ALL cells with 5′ Notch1 deletions (T-ALL48, T-ALL5) grew independent of ligand expression (Fig. S7). Here, NOTCH1 is linked to acute lymphoblastic leukemia.