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

The BCR-ABL1 mRNA fusion junction is a unique nucleotide sequence created by the reciprocal translocation between chromosomes 9 and 22, known as the Philadelphia chromosome (Ph) [StatPearls, 2023]. This genetic event fuses the Breakpoint cluster region (BCR) gene with the Abelson murine leukemia viral oncogene homolog 1 (ABL1) gene, resulting in a chimeric transcript that encodes the BCR-ABL1 oncoprotein [NCI, 2024]. This protein is a constitutively active tyrosine kinase that drives the pathogenesis of Chronic Myeloid Leukemia (CML) and a subset of Acute Lymphoblastic Leukemia (ALL) by activating downstream signaling pathways like JAK/STAT and PI3K/AKT [PubMed, 2015]. While the protein product is the primary clinical target for small-molecule tyrosine kinase inhibitors (TKIs) such as imatinib and asciminib, the mRNA junction itself serves as a highly specific target for molecular diagnostics and experimental RNA-interference (RNAi) therapies [Blood, 2003]. Monitoring the levels of this fusion transcript via quantitative RT-PCR is the gold standard for assessing treatment response and minimal residual disease in patients [NIH, 2022]. Therapeutic strategies targeting the mRNA junction, such as antisense oligonucleotides or siRNA, aim to selectively silence the oncogene without affecting the normal physiological functions of the wild-type BCR or ABL1 genes [Journal of Clinical Investigation, 2007].

Other names

BCR-ABL fusion mRNAPhiladelphia chromosome transcriptb2a2 fusion transcriptb3a2 fusion transcripte1a2 fusion transcriptBCR-ABL1 junctional sequence

Small molecule inhibition of the BCR-ABL1 tyrosine kinase protein product; experimental therapeutic approaches include antisense oligonucleotide (ASO) or siRNA-mediated degradation of the mRNA fusion junction to prevent translation.