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]. This evidence concerns the gene STAT5B and chronic myelogenous leukemia, BCR-ABL1 positive.