Chronic myeloid leukemia (CML) is characterized by the presence of a constitutively active Abl kinase, which is the product of a chimeric BCR-ABL gene, caused by the genetic translocation known as the Philadelphia chromosome. Imatinib, a selective inhibitor of the Bcr-Abl tyrosine kinase, has significantly improved the clinical outcome of patients with CML. However, subsets of patients lose their response to treatment through the emergence of imatinib-resistant cells, and imatinib treatment is less durable for patients with late stage CML. Although alternative Bcr-Abl tyrosine kinase inhibitors have been developed to overcome drug resistance, a cocktail therapy of different kinase inhibitors and additional chemotherapeutics may be needed for complete remission of CML in some cases. Chlorambucil has been used for treatment of B cell chronic lymphocytic leukemia, non-Hodgkin's and Hodgkin's disease. Here we report that a DNA sequence-specific pyrrole-imidazole polyamide-chlorambucil conjugate, 1R-Chl, causes growth arrest of cells harboring both unmutated BCR-ABL and three imatinib resistant strains. 1R-Chl also displays selective toxicities against activated lymphocytes and a high dose tolerance in a murine model.
Chronic myeloid leukemia ( CML ) is characterized by the presence of a constitutively active Abl kinase , which is the product of a chimeric BCR - ABL gene , caused by the genetic translocation known as the Philadelphia chromosome . Imatinib , a selective inhibitor of the Bcr - Abl tyrosine kinase , has significantly improved the clinical outcome of patients with CML . However , subsets of patients lose their response to treatment through the emergence of imatinib - resistant cells , and imatinib treatment is less durable for patients with late stage CML . Although alternative Bcr - Abl tyrosine kinase inhibitors have been developed to overcome drug resistance , a cocktail therapy of different kinase inhibitors and additional chemotherapeutics may be needed for complete remission of CML in some cases . Chlorambucil has been used for treatment of B cell chronic lymphocytic leukemia , non - Hodgkin 's and Hodgkin 's disease . Here we report that a DNA sequence - specific pyrrole - imidazole polyamide - chlorambucil conjugate , 1R - Chl , causes growth arrest of cells harboring both unmutated BCR - ABL and three imatinib resistant strains . 1R - Chl also displays selective toxicities against activated lymphocytes and a high dose tolerance in a murine model .
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