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

BCR–ABL1 tyrosine kinase is an abnormal fusion protein formed by the reciprocal translocation t(9;22)(q34;q11), generating the Philadelphia chromosome in hematopoietic cells[1][2][4]. This fusion combines the N-terminus of the BCR gene with the ABL1 tyrosine kinase domain, resulting in a constitutively active kinase that drives uncontrolled proliferation, impaired apoptosis, and leukemogenesis, especially in chronic myeloid leukemia and some acute lymphoblastic leukemias[1][2][4]. The discovery of BCR–ABL1's causative role enabled the development of tyrosine kinase inhibitors—such as imatinib and second- and third-generation agents—that specifically inhibit its kinase activity and fundamentally transformed the prognosis of Philadelphia chromosome–positive leukemias[2][3][4][6]. Nevertheless, challenges such as resistance mutations, long-term toxicity, and disease persistence necessitate ongoing development of improved inhibitors and therapeutic strategies[2][4][6].

Other names

BCR–ABL1 fusion proteinBCR–ABL1 oncoproteinBCR–ABL tyrosine kinasePhiladelphia chromosome fusion proteinp210BCR–ABL (most common isoform in CML)p190BCR–ABL (common in some ALL)

ATP-competitive inhibition of BCR–ABL1 kinase activity (imatinib, dasatinib, nilotinib, bosutinib, ponatinib) Allosteric inhibition of the myristoyl pocket (asciminib)