Chronic myelogenous leukemia (CML) is a clonal hematopoietic disorder caused by the reciprocal translocation between chromosome 9 and 22. As a result of this translocation, a novel fusion gene, BCR-ABL, is created on Philadelphia (Ph) chromosome, and the constitutive activity of the BCR-ABL protein tyrosine kinase plays a critical role in the disease pathogenesis. Imatinib mesylate, a selective BCR-ABL tyrosine kinase inhibitor, was first given to a patient with CML in June 1998. Since then, it has continued to demonstrate remarkable efficacy in treating patients with CML. Based upon the results of early phase I and II studies, a phase III study (IRIS Study) that was randomized to first-line imatinib (400 mg/day) or to standard treatment with interferon+low-dose Ara-C, was conducted on 1,106 patients newly diagnosed (within 6 months) with chronic-phase CML. After median follow-up of 30 months, imatinib showed significantly superior tolerability, hematologic and cytogenetic responses (major cytogenetic response, 90%; complete cytogenetic response, 82%), and overall survival (95% without censoring allo-HSCT). Although imatinib is the first-line therapy and has changed the paradigm of CML treatment strategy, questions remain as to the meaning of cytogenetic and molecular response, curability, optimal dose, and relation with allo-HSCT.
Chronic myelogenous leukemia ( CML ) is a clonal hematopoietic disorder caused by the reciprocal translocation between chromosome 9 and 22 . As a result of this translocation , a novel fusion gene , BCR - ABL , is created on Philadelphia ( Ph ) chromosome , and the constitutive activity of the BCR - ABL protein tyrosine kinase plays a critical role in the disease pathogenesis . Imatinib mesylate , a selective BCR - ABL tyrosine kinase inhibitor , was first given to a patient with CML in June 1998 . Since then , it has continued to demonstrate remarkable efficacy in treating patients with CML . Based upon the results of early phase I and II studies , a phase III study ( IRIS Study ) that was randomized to first - line imatinib ( 400 mg / day ) or to standard treatment with interferon+low - dose Ara - C , was conducted on 1,106 patients newly diagnosed ( within 6 months ) with chronic - phase CML . After median follow - up of 30 months , imatinib showed significantly superior tolerability , hematologic and cytogenetic responses ( major cytogenetic response , 90 % ; complete cytogenetic response , 82 % ) , and overall survival ( 95 % without censoring allo - HSCT ) . Although imatinib is the first - line therapy and has changed the paradigm of CML treatment strategy , questions remain as to the meaning of cytogenetic and molecular response , curability , optimal dose , and relation with allo - HSCT .
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