Our data provide the first proof of direct regulatory relationship between BCR-ABL, c-MYB and ESPL1/Separase and give a plausible mechanistic explanation on how BCR-ABL may trigger dislocation between the centrosome-centriole cycle and the cell cycle in CML contributing to clonal evolution and genomic instability. The gene discussed is ABL1; the disease is chronic myelogenous leukemia, BCR-ABL1 positive.