The identification of the Philadelphia chromosome and the subsequent discovery that it represents a translocation between the long arms of chromosomes 9 and 22 producing an aberrant tyrosine kinase, known as BCR-ABL1, has catalyzed our understanding and treatment of this hematologic malignancy.     ///    These inhibitors appear effective in inhibiting most of the mutant BCR-ABL1 molecules that are resistant to IM.     ///    "The dominant mechanism appears to be mutations in the kinase domain of BCR-ABL1, which result in altered affinity of IM for the BCR-ABL1 protein. "    ///    "An extensive search for molecules to block the aberrant BCR-ABL1 protein resulted in the development of IM as an orally bioavailable agent with remarkable efficacy in producing hematologic, cytogenetic, and molecular remissions. "