Structure and Dynamics of the ABL1 Tyrosine Kinase and Its Important Role in Chronic Myeloid Leukemia

Abelson (ABL1) tyrosine kinase is an essential component of non-receptor tyrosine kinases and is associated with numerous cellular processes, including differentiation and proliferation. The structural features of ABL1 include a distinct N-terminal cap region, a C-terminal tail, a bilobed kinase, SH2, and SH3 domains. These domains enable its engagement in several signaling cascades and dynamic control. The pathophysiology of chronic myeloid leukemia (CML) is mainly driven by the BCR-ABL1 oncoprotein, arising from dysregulation of ABL1 kinase, namely through its fusion to the breakpoint cluster region (BCR) gene. ABL1 is a crucial target in the treatment of CML as the BCR-ABL1 fusion causes uncontrolled cellular proliferation and resistance to apoptosis. Tyrosine kinase inhibitors (TKIs) targeting the ABL1 tyrosine kinase are playing a critical role in the treatment of CML through the inhibition of persistently activated signaling pathways mediated by the BCR-ABL1 fusion protein. The article examines the structural characteristics of ABL1, how they relate to CML, and the interactions between ABL1 and the current FDA-approved TKIs, emphasizing the kinase's critical function in carcinogenesis and its possible target status for tyrosine kinase inhibitors.