Secondly, newly acquired alterations might circumvent the inhibitory effect of a given drug; for instance, the accumulation of various new genetic abnormalities in CML result in the activation of signaling pathways independent of BCR-ABL activity and consequently facilitates disease progression to blast crisis [41, 43, 44]. This evidence concerns the gene ABL1 and chronic myelogenous leukemia, BCR-ABL1 positive.