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

The Breakpoint cluster region–Abelson murine leukemia viral oncogene 1 fusion protein (BCR–ABL1) is an abnormal tyrosine kinase created by the translocation t(9;22)(q34;q11), known as the Philadelphia chromosome, which fuses the BCR gene on chromosome 22 to the ABL1 gene on chromosome 9[5][1]. The resulting fusion protein contains functional domains from both BCR (including a coiled-coil oligomerization domain) and ABL1 (including SH2, SH3, and tyrosine kinase domains)[1][3][4]. This fusion abrogates the normal autoregulatory mechanisms of ABL1, leading to **constitutive tyrosine kinase activity** that drives uncontrolled proliferation, resistance to apoptosis, and aberrant signaling in hematopoietic cells[1][2][3][4]. BCR–ABL1 is the primary molecular driver of chronic myeloid leukemia and is also found in a subset of acute lymphoblastic leukemias. The discovery of this fusion enabled the development of targeted tyrosine kinase inhibitors such as imatinib, which have transformed the treatment and prognosis of CML and related disorders[1][3][5]. Monitoring BCR–ABL1 transcript levels is central to disease management, while mutation-driven resistance and adverse effects of kinase inhibition represent major clinical challenges[1][3].

Other names

BCR-ABL1 fusion proteinPhiladelphia chromosome fusion proteinBCR::ABL1p210 BCR–ABLp185 BCR–ABL

Tyrosine kinase inhibition; Competitive inhibition of ATP binding; Allosteric inhibition (e.g., asciminib); Induction of apoptosis in leukemic cells