Chronic myelogenous leukemia (CML) is characterized by the presence of a Bcr-Abl fusion protein with deregulated tyrosine kinase activity that is required for maintaining the malignant phenotype. Imatinib, a selective inhibitor of Bcr-Abl, induces major cytogenetic remission (MCR) or complete cytogenetic remission (CCR) in the majority of patients with CML in first chronic phase. However, thorough re-evaluation of cytogenetics in a cohort of patients in MCR or CCR demonstrated clonal karyotypic abnormalities in more than 10% of cases, some of which were clinically associated with a myelodysplastic syndrome (MDS). Further analysis identified previous exposure to cytarabine and idarubicin as significant risk factors for the subsequent occurrence of abnormalities in Philadelphia chromosome-negative (Ph-) cells. To investigate if cytogenetically normal but clonal hematopoiesis might be present in other patients in cytogenetic remission, we studied X-chromosome inactivation as a marker of clonality by polymerase chain reaction analysis of the human androgen receptor (HUMARA). We find that imatinib restores a polyclonal pattern in most patients in CCR and MCR. Nonetheless, our results are consistent with the notion that targeted therapy of CML with imatinib favors the manifestation of Ph- clonal disorders in some patients. They indicate that patients on imatinib should be followed with conventional cytogenetics, even after induction of CCR.
Chronic myelogenous leukemia ( CML ) is characterized by the presence of a Bcr - Abl fusion protein with deregulated tyrosine kinase activity that is required for maintaining the malignant phenotype . Imatinib , a selective inhibitor of Bcr - Abl , induces major cytogenetic remission ( MCR ) or complete cytogenetic remission ( CCR ) in the majority of patients with CML in first chronic phase . However , thorough re - evaluation of cytogenetics in a cohort of patients in MCR or CCR demonstrated clonal karyotypic abnormalities in more than 10 % of cases , some of which were clinically associated with a myelodysplastic syndrome ( MDS ) . Further analysis identified previous exposure to cytarabine and idarubicin as significant risk factors for the subsequent occurrence of abnormalities in Philadelphia chromosome - negative ( Ph- ) cells . To investigate if cytogenetically normal but clonal hematopoiesis might be present in other patients in cytogenetic remission , we studied X - chromosome inactivation as a marker of clonality by polymerase chain reaction analysis of the human androgen receptor ( HUMARA ) . We find that imatinib restores a polyclonal pattern in most patients in CCR and MCR . Nonetheless , our results are consistent with the notion that targeted therapy of CML with imatinib favors the manifestation of Ph- clonal disorders in some patients . They indicate that patients on imatinib should be followed with conventional cytogenetics , even after induction of CCR .
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