BCR-ABL Tyrosine-Protein Kinase

BCR-ABL tyrosine-protein kinase is a chimeric oncoprotein resulting from the fusion of the BCR and ABL1 genes. This fusion, known as the Philadelphia chromosome, is most commonly associated with chronic myelogenous leukemia (CML), where it drives disease pathogenesis by constitutively activating tyrosine kinase signaling pathways. The resulting BCR-ABL kinase becomes constitutively active leading to uncontrolled cell proliferation and resistance to apoptosis. Bcr-Abl tyrosine kinase inhibitors (TKIs), such as imatinib, nilotinib, and dasatinib, are first-line therapies for CML but may encounter resistance due to mutations within the Abl kinase domain or other mechanisms.

Selective inhibition of BCR-ABL tyrosine kinase activity