Imatinib mesylate (IM) binds to the BCR-ABL protein, inhibiting its kinase 
activity and effectively controlling diseases driven by this kinase. IM 
resistance has been associated with kinase mutations or increased BCR-ABL 
expression. However, disease progression may be mediated by other mechanisms 
that render tumor cells independent of BCR-ABL. To demonstrate this potential, 
IM-resistant cells were found in chronic myelogenous leukemia patients with 
continuous BCR-ABL gene expression but undetectable BCR-ABL protein expression. 
These cells were unresponsive to IM and acquired BCR-ABL-independent signaling 
characteristics. IM resistance in some patients may be mediated through loss of 
kinase target dependence.