BCR-ABL is a fusion gene that arises as a result of a chromosomal translocation between the Philadelphia chromosome (Ph) and the Abelson tyrosine kinase (ABL) gene. This genetic abnormality is typically associated with certain types of leukemia, particularly chronic myeloid leukemia (CML).
When the BCR-ABL fusion gene is formed, it produces a chimeric protein that exhibits an abnormally high tyrosine kinase activity. This dysregulated tyrosine kinase activity leads to the development and progression of CML by stimulating uncontrolled proliferation of myeloid cells.
The constitutive activation of BCR-ABL protein results in the disruption of normal cellular signaling pathways, promoting cell growth, survival, and inhibition of apoptosis. Additionally, BCR-ABL alters the adhesion properties of leukemia cells, allowing them to infiltrate various tissues and organs.
Targeted therapy against BCR-ABL has revolutionized the treatment of CML. Medications known as tyrosine kinase inhibitors (TKIs), such as imatinib, dasatinib, and nilotinib, are commonly used to inhibit the activity of BCR-ABL. These drugs specifically target the altered tyrosine kinase activity, thereby suppressing the proliferation of leukemia cells and inducing their apoptosis.
Regular monitoring of BCR-ABL levels by molecular tests is crucial for assessing treatment response and disease progression in individuals with CML. Lowering the BCR-ABL transcript levels to an undetectable level, referred to as a complete molecular response, is the primary treatment goal. Achieving and maintaining this milestone provides an excellent long-term prognosis for patients with CML.
