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

BCR-ABL1 is a chimeric fusion protein resulting from the reciprocal translocation between chromosomes 9 and 22, commonly referred to as the Philadelphia chromosome [1.1.1, 1.2.1]. This genetic event fuses the Breakpoint Cluster Region (BCR) gene with the Abelson murine leukemia viral oncogene homolog 1 (ABL1) gene, creating a constitutively active non-receptor tyrosine kinase [1.1.1, 1.1.3]. The resulting oncoprotein drives oncogenic signaling through pathways such as PI3K/AKT, JAK/STAT, and RAS/MAPK, which promote uncontrolled cell proliferation and resistance to apoptosis [1.1.1, 1.1.2]. BCR-ABL1 is the hallmark driver of chronic myeloid leukemia (CML) and is also found in a significant percentage of adult acute lymphoblastic leukemia (ALL) cases [1.1.1, 1.1.3]. As a therapeutic target, it is inhibited by a class of drugs known as tyrosine kinase inhibitors (TKIs), which bind to the ATP-binding site or allosteric pockets of the kinase domain [1.1.2, 1.1.1]. While TKIs like imatinib have transformed CML into a manageable chronic condition, the emergence of resistance mutations, such as the T315I gatekeeper mutation, remains a significant clinical challenge [1.1.1, 1.1.4]. Monitoring BCR-ABL1 transcript levels via quantitative PCR is the standard method for assessing treatment response and detecting early signs of relapse [1.1.4, 1.2.4].

Other names

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

Tyrosine kinase inhibition via ATP-competitive binding or allosteric modulation (STAMP inhibition)