Bcr-Abl fusion protein tyrosine kinase

The Bcr-Abl fusion protein tyrosine kinase is an abnormal, constitutively active enzyme resulting from the fusion of the breakpoint cluster region (BCR) gene on chromosome 22 and the Abelson murine leukemia viral oncogene homolog 1 (ABL1) gene on chromosome 9. This genetic event creates a chimeric oncogene known as BCR-ABL, which encodes a protein with deregulated tyrosine kinase activity. The presence of this fusion protein is most commonly associated with chronic myelogenous leukemia (CML), but it can also be found in some cases of acute lymphoblastic leukemia (ALL) and rarely in acute myeloid leukemia (AML). Constitutive activation of this tyrosine kinase underlies uncontrolled growth of leukemic cells. First-line therapy involves selective inhibition using small-molecule tyrosine kinase inhibitors (TKIs), such as imatinib; second-generation TKIs have been developed to overcome resistance mutations within the Abl kinase domain or other mechanisms like overexpression or activation of alternative pathways.

Other names

BCR-ABLp210Bcr-Ablp185Bcr-AblPhiladelphia chromosome translocationBCR-ABL1

Selective inhibition using small-molecule tyrosine kinase inhibitors (TKIs).