Breakpoint cluster region–Abelson murine leukemia viral oncogene homolog 1 fusion protein (BCR-ABL1)

**The BCR-ABL1 fusion protein** is a constitutively active cytoplasmic tyrosine kinase generated by the reciprocal translocation between chromosomes 9 and 22 (“Philadelphia chromosome”). This results in the N-terminal region of the BCR protein being fused to the C-terminal region of the ABL1 kinase. Multiple isoforms exist depending on the breakpoint (most commonly p210 in CML, p185 in ALL). The fusion disables autoinhibitory control of ABL1, resulting in sustained kinase activity that phosphorylates multiple downstream effectors, driving growth factor–independent signal transduction, excessive cell proliferation, impaired apoptosis, and altered cytoskeletal organization. These oncogenic properties render it the principal molecular driver of chronic myeloid leukemia and a subset of acute lymphoblastic leukemia cases. Targeted inhibition of BCR-ABL1 with tyrosine kinase inhibitors has revolutionized therapy for these diseases[1][2][3][5][6].

Other names

BCR-ABL1 fusion proteinBCR::ABL1BCR-ABLPhiladelphia chromosome fusion proteinp210 BCR-ABLp185 BCR-ABLp230 BCR-ABLt(9;22) fusion protein

Competitive inhibition of ATP binding at the tyrosine kinase domain - Allosteric inhibition (as with asciminib) - Destabilization of active kinase conformation