Breakpoint Cluster Region-Abelson Murine Leukemia Viral Oncogene Homolog 1 Tyrosine Kinase (BCR-ABL)

BCR-ABL is a constitutively active, chimeric tyrosine kinase resulting from a reciprocal translocation between chromosomes 9 and 22—t(9;22)(q34;q11)—which creates the Philadelphia chromosome. This fusion gene is characteristic of Philadelphia chromosome-positive leukemias, most notably chronic myeloid leukemia (CML), but also found in some cases of acute lymphoblastic leukemia (ALL) and chronic neutrophilic leukemia (CNL). Targeting the ATP-binding site within the ABL kinase domain has led to the development of tyrosine kinase inhibitors (TKIs), revolutionizing treatment for Ph+ leukemias. However, resistance can develop due to mutations within the ABL kinase domain or other mechanisms such as overexpression or activation of alternative pathways.

Other names

p210 BCR-ABLp185 BCR-ABLp230 BCR-ABLPhiladelphia chromosome

Inhibition of BCR-ABL tyrosine kinase activity by binding to the ATP-binding site, thus blocking downstream signaling pathways.