Breakpoint Cluster Region–Abelson Murine Leukemia Viral Oncogene Fusion

The BCR–ABL fusion protein is an abnormal tyrosine kinase produced by the fusion of the BCR gene on chromosome 22 and the ABL gene on chromosome 9. This genetic rearrangement, known as the Philadelphia chromosome, is a hallmark of chronic myeloid leukemia (CML) and also occurs in other leukemias. The fusion protein contains domains from both parent proteins, with the BCR portion enabling self-association and constitutive activation of the ABL tyrosine kinase. This leads to persistent phosphorylation of downstream signaling proteins and uncontrolled cell division, characteristic of leukemias. Targeted therapies such as imatinib specifically inhibit the ATP binding site within the ABL tyrosine kinase portion, effectively treating CML by blocking aberrant signaling.

Inhibition of ATP binding to the ABL tyrosine kinase domain, blocking aberrant signaling