NOTCH1 and acute lymphoblastic leukemia: To this end, we pursued four lines of investigation: (1) genetic engineering of the T-ALL model to humanize the spectrum of the murine Notch1 mutations; (2) the preclinical testing of Notch1-targeting therapeutic antibodies correlative to the Notch1 mutational status; (3) the assessment of Notch3 signaling contribution to leukemogenesis; and (4) the establishment of leukemic disease in fully immunocompetent, syngeneic host mice for the therapeutic testing of immune checkpoint blockade.