The development of ABL1 KD mutations is the dominant mechanism of resistance in patients with Ph + ALL, with T315I mutations detected in up to 75% of patients at the time of relapse after treatment with a first- or second-generation BCR-ABL1 TKI, neither of which have clinical activity against these T315I mutations2,5,6. Here, ABL1 is linked to acute lymphoblastic leukemia.