Abelson murine leukemia viral oncogene homolog 1 (ABL1) and Breakpoint cluster region-Abelson fusion protein (BCR-ABL1) (ABL1 / BCR-ABL1)

The Abl/BCR-ABL ATP site is the catalytic pocket of the Abelson murine leukemia viral oncogene homolog 1 (ABL1) and its oncogenic fusion counterpart, BCR-ABL1 [1, 2]. ABL1 is a non-receptor tyrosine kinase that normally regulates cell growth, survival, and DNA repair [2, 5]. The BCR-ABL1 fusion, resulting from the Philadelphia chromosome translocation t(9;22), is constitutively active and drives the pathogenesis of chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) [3, 4]. Drugs targeting this site, known as tyrosine kinase inhibitors (TKIs), compete with ATP to block the phosphorylation of downstream substrates, thereby inhibiting oncogenic signaling and inducing apoptosis in leukemic cells [4, 8]. While first-generation TKIs like imatinib revolutionized treatment, resistance often emerges through point mutations within the ATP-binding domain, most notably the T315I gatekeeper mutation [1, 7]. Subsequent generations of TKIs, such as dasatinib, nilotinib, and ponatinib, were developed to overcome these mutations, though they carry specific safety profiles including risks of cardiotoxicity and pleural effusion [10, 11].

Other names

c-Ablp210 BCR-ABLp190 BCR-ABLPhiladelphia chromosome proteinAbelson tyrosine-protein kinase 1BCR-ABL1 tyrosine kinase

Tyrosine kinase inhibition (ATP-competitive)