BCR-ABL1 fusion oncoprotein (BCR-ABL1)

The BCR-ABL1 fusion oncoprotein results from the t(9;22) Philadelphia chromosome translocation, fusing BCR (chromosome 22) sequences including the N-terminal coiled-coil oligomerization domain with the tyrosine kinase domain of ABL1 (chromosome 9), leading to constitutive kinase activation. Variants include p210 (BCR exons 13/14 to ABL1 exon 1, predominant in chronic myeloid leukemia), p190 (BCR exon 1 to ABL1 exon 2, common in acute lymphoblastic leukemia), and p230 (BCR exon 19 to ABL1 exon 2, neutrophilic CML). The coiled-coil domain promotes dimerization/tetramerization, enhancing kinase activity and downstream signaling via RAS/MAPK, STAT5, PI3K/AKT, SRC family kinases, promoting cell proliferation, growth factor independence, anti-apoptosis (e.g., via Bcl-2), actin association, ROS-induced DNA damage, and genomic instability. BCR contributes additional domains like putative serine/threonine kinase and RhoGEF for modulation.

Other names

p210BCR-ABLp190BCR-ABLp230BCR-ABLPhiladelphia chromosome fusion proteinbcr-abl fusion protein

Tyrosine kinase inhibition, Constitutive kinase activity blockade via oligomerization disruption