Breakpoint cluster region-Abelson murine leukemia viral oncogene homolog 1 (BCR-ABL1) (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 (Source: NIH National Cancer Institute). This fusion creates a constitutively active non-receptor tyrosine kinase that drives the pathogenesis of Chronic Myeloid Leukemia (CML) and a subset of Acute Lymphoblastic Leukemia (ALL) by activating signaling pathways like JAK/STAT, PI3K/AKT, and Ras/MAPK (Source: UniProt P00519). These pathways promote uncontrolled cell proliferation and inhibit apoptosis in hematopoietic stem cells. The Ba/F3 cell line is a murine pro-B cell model frequently used in drug discovery; when engineered to express BCR-ABL1, these cells lose their dependency on interleukin-3 (IL-3), providing a robust system to evaluate the potency of tyrosine kinase inhibitors (Source: PubMed PMID: 12738670). While tyrosine kinase inhibitors (TKIs) like imatinib have revolutionized treatment, the emergence of kinase domain mutations, such as the gatekeeper T315I mutation, remains a primary cause of therapeutic failure and disease progression (Source: PubMed PMID: 17400277). The input provided, "Ba/F3 cells expressing wild-type BCR-ABL1," refers to this specific cellular assay system used to screen for drug efficacy against the non-mutated form of the kinase rather than the molecular target itself.

Other names

Philadelphia chromosomep210 BCR-ABLp190 BCR-ABLBCR-ABL tyrosine kinaseBCR-ABL1 fusion protein

Inhibition of the BCR-ABL1 tyrosine kinase activity by competing with ATP for the binding site (Type I and II inhibitors) or through allosteric modulation at the myristoyl binding site, thereby blocking downstream oncogenic signaling pathways (Source: PubMed PMID: 12738670).