Abelson tyrosine-protein kinase 1 (ABL1) and Breakpoint cluster region-Abelson tyrosine kinase (BCR-ABL1) fusion protein (ABL1 / BCR-ABL1)

Abelson tyrosine-protein kinase 1 (ABL1) is a non-receptor tyrosine kinase that functions as a critical regulator of cell growth, survival, and DNA damage responses [1, 4]. In hematopoietic cells, a reciprocal translocation between chromosomes 9 and 22 results in the formation of the Philadelphia chromosome and the subsequent production of the BCR-ABL1 fusion protein [10, 11]. This chimeric protein possesses constitutive tyrosine kinase activity, which drives the uncontrolled proliferation and survival of leukemic cells, serving as the primary oncogenic driver in Chronic Myeloid Leukemia (CML) and a subset of Acute Lymphoblastic Leukemia (ALL) [2, 6]. The development of small-molecule tyrosine kinase inhibitors (TKIs) that target the ATP-binding site or the myristoyl pocket of BCR-ABL1 has revolutionized the treatment of these diseases, turning them into manageable chronic conditions [5, 13]. Despite this success, therapeutic challenges persist, including the emergence of resistance mutations such as T315I and significant safety concerns like cardiotoxicity and pleural effusion [15, 18, 20].

Other names

c-AblAbelson murine leukemia viral oncogene homolog 1Philadelphia chromosomePh+p210 BCR-ABL1p190 BCR-ABL1p230 BCR-ABL1JTK7p150

Tyrosine kinase inhibition (ATP-competitive) and Allosteric inhibition (Myristoyl pocket binding)