Breakpoint cluster region–Abelson murine leukemia viral oncogene fusion protein (BCR-ABL fusion protein)

The BCR-ABL fusion protein arises from a reciprocal translocation between chromosomes 9 and 22, resulting in the so-called Philadelphia chromosome, and encodes a constitutively active tyrosine kinase that is central to the pathogenesis of chronic myeloid leukemia (CML) and several forms of acute lymphoblastic leukemia[1][3][6]. The fusion protein combines N-terminal sequences of the breakpoint cluster region (BCR) gene with the catalytic and regulatory domains of the Abelson murine leukemia viral oncogene (ABL1), leading to loss of normal autoinhibitory control and continuous activation of downstream signaling. This causes uncontrolled proliferation, inhibition of apoptosis, altered cell adhesion, and migratory properties in hematopoietic stem/progenitor cells[1][3][4]. Multiple targeted drugs (tyrosine kinase inhibitors) have been developed and clinically approved to inhibit BCR-ABL, transforming CML from a fatal to a chronic disease in most patients. Therapeutic challenges include the emergence of resistance mutations, particularly in the ABL kinase domain[3]. Note: - The query also mentioned “SRC-family kinases.” These are a distinct, related family of non-receptor tyrosine kinases (e.g., SRC, LYN, FYN). BCR-ABL can activate SRC-family kinases, and some TKIs (notably dasatinib) also inhibit SRC-family kinases, but “BCR/ABL fusion protein, SRC-family kinases” is not a standard single molecular target. If structured information about SRC-family kinases is needed, this should be handled as a separate target. - BCR-ABL, not “BCR/ABL fusion protein, SRC-family kinases,” should be used as the canonical target entry. - SRC-family kinases are frequently co-targeted in some leukemia therapies due to their role in disease progression and signaling cross-talk with BCR-ABL, but these are biochemically and genetically distinct[3].

Other names

BCR-ABLBCR-ABL1BCR/ABL fusion proteinPhiladelphia chromosome fusion protein

ATP-competitive inhibition of kinase activity; Allosteric inhibition (e.g., asciminib); Induction of proteasomal degradation (e.g., via HSP90 inhibition)