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

BCR-ABL1 is a constitutively active tyrosine kinase formed by the reciprocal translocation between chromosomes 9 and 22, known as the Philadelphia chromosome (StatPearls, 2023). This fusion protein combines the Breakpoint Cluster Region (BCR) with the Abelson murine leukemia viral oncogene homolog 1 (ABL1), leading to unregulated signaling that drives uncontrolled cell proliferation and survival (UniProt, 2024). It is the primary driver of chronic myeloid leukemia (CML) and a subset of acute lymphoblastic leukemia (ALL) (NCI, 2023). The kinase activates multiple downstream pathways, including PI3K/AKT, RAS/MAPK, and STAT, which promote leukemogenesis (PubMed, PMC7073331). Therapeutic targeting of BCR-ABL1 with tyrosine kinase inhibitors (TKIs) like imatinib has revolutionized the treatment of CML, turning it into a manageable chronic condition (NIH, 2022). However, the emergence of resistance mutations, most notably the T315I gatekeeper mutation, remains a significant clinical challenge requiring next-generation or allosteric inhibitors like asciminib (Nature, 2021).

Other names

Philadelphia chromosomep210 BCR-ABLp190 BCR-ABLp230 BCR-ABLBCR-ABL1 fusion proteinBreakpoint cluster region-Abelson murine leukemia viral oncogene homolog 1

ATP-competitive inhibition of the tyrosine kinase domain and allosteric inhibition of the ABL myristoyl pocket (StatPearls, 2023; Nature, 2021).