BCR and chronic myelogenous leukemia, BCR-ABL1 positive: Recognized modes of resistance in CML LSCs to TKIs include the following: (a) primary and secondary (cell selection under treatment pressure) mutations of BCR/ABL, affecting TKI binding to the BCR/ABL tyrosine kinase domain; (b) amplification of BCR/ABL; (c) enhanced activity of drug exporters; (d) quiescence; (e) mutations outside BCR/ABL, determining BCR/ABL-independent survival and proliferation (mutation-driven loss of “oncogene addiction”); and (f) BCR/ABL protein suppression in cells expressing the BCR/ABL gene [14,66].