BCR-ABL tyrosine kinase (BCR-ABL) (BCR-ABL)

The BCR-ABL oncoprotein is a constitutively active tyrosine kinase resulting from a reciprocal translocation between chromosomes 9 and 22, known as the Philadelphia chromosome (t(9;22)(q34;q11)) (StatPearls, 2023). This fusion protein combines the Breakpoint Cluster Region (BCR) with the Abelson murine leukemia viral oncogene homolog 1 (ABL1), leading to the loss of the ABL1 auto-inhibitory domain (UniProt, 2024). The resulting aberrant kinase activity triggers multiple downstream signaling pathways, including PI3K/AKT, RAS/MAPK, and JAK/STAT, which drive uncontrolled cell proliferation and inhibit apoptosis in hematopoietic stem cells (PubMed, PMID: 28438744). BCR-ABL is the primary driver of Chronic Myeloid Leukemia (CML) and is also found in a subset of Acute Lymphoblastic Leukemia (ALL) cases (NCI, 2024). Pharmacological targeting of BCR-ABL with tyrosine kinase inhibitors (TKIs) like imatinib has revolutionized treatment, significantly improving patient survival (NIH, 2023). However, the emergence of point mutations in the kinase domain, most notably the T315I gatekeeper mutation, remains a significant therapeutic challenge, necessitating the development of next-generation and allosteric inhibitors like asciminib (Nature Reviews Cancer, 2021).

Other names

BCR-ABL1Philadelphia chromosome fusion proteinp210 BCR-ABLp190 BCR-ABLp230 BCR-ABL

Tyrosine kinase inhibition via competitive binding to the ATP-binding site or allosteric binding to the myristoyl pocket (FDA, 2021; PubMed, PMID: 30275464).