BCR-ABL kinase (BCR-ABL)

BCR-ABL kinase is a fusion oncoprotein produced by the t(9;22)(q34;q11) translocation, which results in the Philadelphia chromosome seen in CML and some acute leukemias[3][2]. The protein is constitutively active, driving continuous tyrosine kinase activity that triggers signal transduction promoting cell survival, proliferation, angiogenesis, and inhibition of apoptosis[7][3]. Src-family kinases are structurally similar tyrosine kinases with overlapping cellular roles in signaling and oncogenesis; some drugs used for BCR-ABL also inhibit Src-family kinases[1][4]. BCR-ABL and Src-family kinases are major molecular targets for tyrosine kinase inhibitor therapies, with drugs like imatinib, dasatinib, and ponatinib reversing leukemic phenotypes and restoring normal cell function, but resistance mutations—especially T315I—pose therapeutic challenges[4][2]. Key biomarkers for therapy and monitoring are the Philadelphia chromosome and BCR-ABL transcript levels[3][2]. Safety concerns involve drug resistance, off-target effects, and adverse events from broader kinase inhibition[4].

Other names

BCR-ABL fusion proteinPhiladelphia chromosome kinaseBCR::ABLp210BCR-ABLp190BCR-ABLAbl kinasec-AblSrc-family (for Src-family kinases)

- ATP-competitive inhibition of kinase activity (for most TKIs)[4] - Induced protein degradation via HSP90 inhibition[3]