Cancer is thought to arise from multiple genetic events that establish irreversible malignancy. A different mechanism might be present in certain leukaemias initiated by a chromosomal translocation. We have taken a new approach to determine if ablation of the genetic abnormality is sufficient for reversion by generating a conditional transgenic model of BCR–ABL1 (also known as BCR–ABL)-induced leukaemia. This oncogene 1 is the result of a reciprocal translocation and is associated with different forms of leukaemia 2. The most common form, p210 BCR–ABL1, is found in more than 90% of patients with chronic myelogenous leukaemia 3, 4 (CML) and in up to 15% of adult patients with de novoacute lymphoblastic leukaemia 5 (ALL). Efforts to establish a useful transgenic model have been hampered by embryonic lethality when the oncogene is expressed during embryogenesis 6, 7, by reduced penetrance or by extremely long latency periods 8, 9. One model uses the ‘knock-in’approach to induce leukaemia by p190 BCR–ABL1 (ref. 10). Given the limitations of models with p210, we used a different experimental approach 11. Lethal leukaemia developed within an acceptable time frame in all animals, and complete remission was achieved by suppression of BCR–ABL1expression, even after multiple rounds of induction and reversion. Our results demonstrate that BCR–ABL1is required for both induction and maintenance of leukaemia.