In summary we propose the following model for CML disease progression: In the presence of BCR-ABL1 the increase in STAT5 expression leads to an increased probability to acquire a ROS mediated mutation rendering the BCR-ABL1 kinase less responsive to TKIs, a well-documented phenomenon of CML progression [49]. Here, BCR is linked to chronic myelogenous leukemia, BCR-ABL1 positive.