Supra-threshold amounts of DNA damage and genomic instability that occur as a consequence of BCR-ABL cell autonomous and non-cell-autonomous functions during the course of the disease eventually fuel tumor suppressor barrier inactivation (through selecting for p53 mutations and experimental Atm loss, for example), with the subsequent accelerated progression of untreated CP-CML towards the blast crisis. The gene discussed is ABL1; the disease is chronic myelogenous leukemia, BCR-ABL1 positive.