Abelson tyrosine kinase 1 (ABL1)

Abelson tyrosine kinase 1 (ABL1) is a ubiquitous non-receptor tyrosine kinase that plays a critical role in regulating cell growth, survival, and morphogenesis by relaying signals from the cell surface to the nucleus and cytoskeleton (UniProt P00519). Under physiological conditions, its activity is tightly regulated by internal inhibitory domains; however, the chromosomal translocation known as the Philadelphia chromosome results in the BCR-ABL1 fusion protein, which exhibits constitutive kinase activity (NIH/NCI). This aberrant signaling is the primary driver of Chronic Myeloid Leukemia (CML) and a subset of Acute Lymphoblastic Leukemia (ALL), making it one of the most successful targets in precision oncology (PubMed: 28938117). Therapeutic intervention typically involves small-molecule tyrosine kinase inhibitors (TKIs) that bind to the ATP-binding site or, more recently, allosteric sites to stabilize the inactive conformation of the enzyme (StatPearls: NBK532261). While TKIs like imatinib have revolutionized treatment, clinical challenges remain, including the emergence of resistance mutations such as T315I and off-target toxicities like cardiotoxicity and vascular complications (PubMed: 30237468).

Other names

Tyrosine-protein kinase ABL1c-ABLp150JTK7Abelson murine leukemia viral oncogene homolog 1Proto-oncogene c-Abl

Tyrosine kinase inhibition via ATP-competitive binding or allosteric modulation (specifically at the myristoyl pocket) to prevent phosphorylation of downstream substrates.