Abelson murine leukemia viral oncogene homolog including Bcr-Abl fusion protein (Bcr-Abl)

The Abelson murine leukemia viral oncogene homolog including Bcr-Abl fusion protein, commonly referred to as Bcr-Abl, is a constitutively active tyrosine kinase created by the fusion of the BCR gene on chromosome 22 and the ABL1 gene on chromosome 9. This rearrangement forms the Philadelphia chromosome and produces a chimeric oncoprotein found in the majority of chronic myelogenous leukemia and some other hematologic malignancies. The Bcr-Abl fusion protein leads to increased kinase activity, enhanced cell signaling for proliferation and survival, and resistance to apoptosis, promoting malignant transformation of hematopoietic cells. Multiple molecular isoforms exist (notably p210, p190, and p230), each associated with distinct hematological diseases. Bcr-Abl is the prototypical target for tyrosine kinase inhibitor (TKI) therapy, with several approved drugs such as imatinib and newer agents for resistant forms of the disease. Resistance (especially due to mutations in the kinase domain) and off-target effects remain clinical challenges.

Other names

BCR-ABL fusion proteinBreakpoint cluster region-Abelson fusion proteinPhiladelphia chromosome fusion proteinBcr-Abl1P190 Bcr-AblP210 Bcr-AblP230 Bcr-Abl

ATP-competitive inhibition of the Bcr-Abl kinase domain (e.g., imatinib, dasatinib, nilotinib, bosutinib, ponatinib); Allosteric inhibition of kinase activity (asciminib); Degradation of Bcr-Abl fusion protein (novel experimental approaches); Induction of apoptosis via blocking downstream signaling pathways.