BCR-ABL tyrosine kinase inhibitors, such as imatinib (Gleevec) are highly effective in treating human Philadelphia chromosome-positive (Ph+) chronic myeloid leukaemia (CML) in chronic phase but not in terminal acute phase; acquired drug resistance caused mainly by the development of BCR-ABL kinase domain mutations prevents cure of the leukaemia. In addition, imatinib is ineffective in treating Ph+ B-cell acute lymphoblastic leukaemia (B-ALL) and CML blast crisis, even in the absence of the kinase domain mutations. This type of drug resistance that is unrelated to BCR-ABL kinase domain mutations is caused by the insensitivity of leukaemic stem cells to kinase inhibitors such as imatinib and dasatinib, and by activation of a newly-identified signalling pathway involving SRC kinases that are independent of BCR-ABL kinase activity for activation. This SRC pathway is essential for leukaemic cells to survive imatinib treatment and for CML transition to lymphoid blast crisis. Apart from BCR-ABL and SRC kinases, stem cell pathways must also be targeted for curative therapy of Ph+ leukaemia.
BCR - ABL tyrosine kinase inhibitors , such as imatinib ( Gleevec ) are highly effective in treating human Philadelphia chromosome - positive ( Ph+ ) chronic myeloid leukaemia ( CML ) in chronic phase but not in terminal acute phase ; acquired drug resistance caused mainly by the development of BCR - ABL kinase domain mutations prevents cure of the leukaemia . In addition , imatinib is ineffective in treating Ph+ B - cell acute lymphoblastic leukaemia ( B - ALL ) and CML blast crisis , even in the absence of the kinase domain mutations . This type of drug resistance that is unrelated to BCR - ABL kinase domain mutations is caused by the insensitivity of leukaemic stem cells to kinase inhibitors such as imatinib and dasatinib , and by activation of a newly - identified signalling pathway involving SRC kinases that are independent of BCR - ABL kinase activity for activation . This SRC pathway is essential for leukaemic cells to survive imatinib treatment and for CML transition to lymphoid blast crisis . Apart from BCR - ABL and SRC kinases , stem cell pathways must also be targeted for curative therapy of Ph+ leukaemia .
What tyrosine kinase, involved in a Philadelphia- chromosome positive chronic myelogenous leukemia, is the target of Imatinib (Gleevec)?
What tyrosine kinase , involved in a Philadelphia- chromosome positive chronic myelogenous leukemia , is the target of Imatinib ( Gleevec ) ?
BCR-ABL
BCR-ABL