ABSTRACT
Clinical resistance to imatinib, primarily occurring in advanced-phase Chronic Myeloid Leukemia (CML) and Ph-positive acute lymphoblastic leukemia, stimulated intensive studies to elucidate the mechanisms underlying resistance to imatinib in the clinic. Primary hematologic resistance can be assumed if a patient does not achieve any hematologic response after three months or no complete hematologic response after six month, despite sufficient imatinib treatment. A primary cytogenetic resistance can be defined as a lack of any cytogenetic response after six month of treatment or no complete cytogentic response after 18 month. Meanwhile, mutations conferring clinical resistance to therapeutically used kinase inhibitors were also identified in several other target kinases in various malignant diseases. Breakpoint cluster region-Abelson gene amplification and protein overexpression as causes of imatinib resistance were both identified in vitro as well as in CML patient samples. Clonal cytogenetic evolution is frequently associated with imatinib resistance and has been demonstrated to be an independent poor prognostic factor for survival in CML.
