Initially, Notch mutations were associated with a small subset of T-cell acute lymphoblastic leukemia (T-ALL) patients carrying the chromosomal translocation t(7;9)(q34;q34.3) that, by fusing the 3′ end of NRR-truncated Notch1 gene with the enhancer element of TCRβ gene, leads to constitutive and ligand-independent activation of Notch1 [74]. The gene discussed is NOTCH1; the disease is acute lymphoblastic leukemia.