Tyrosine-protein kinase ABL1 fusion protein

Tyrosine-protein kinase ABL1 fusion proteins arise from chromosomal translocations that fuse the ABL1 gene (on chromosome 9) with another gene, most often BCR (on chromosome 22), forming the Philadelphia chromosome ("BCR-ABL1" fusion), or with other partners in rare cases. These chimeric proteins have constitutive tyrosine kinase activity and drive uncontrolled cell proliferation, survival, and resistance to apoptosis, leading to chronic myeloid leukemia and other hematologic malignancies. Therapeutic inhibitors that specifically target the aberrant kinase activity of ABL1 fusions (e.g., imatinib and next-generation TKIs) have revolutionized the treatment of cancers driven by these fusions

Other names

ABL1 fusion proteinBCR-ABL1ABL1 chimeric proteinPhiladelphia chromosome fusion proteinOncogenic ABL1 fusion

Inhibits ATP binding to active site of ABL kinase domain (competitive inhibition) Prevents phosphorylation of downstream substrates Blocks proliferative and anti-apoptotic signaling in leukemic cells