BCR:ABL1 FUSION GENE: A LANDMARK DISCOVERY IN CANCER BIOLOGY AND TARGETED THERAPY

Abstract

One of the landmark achievements in cancer biology is the discovery of the BCR::ABL1 fusion gene, which remarkably advanced the understanding, diagnosis, and treatment of leukemia. BCR::ABL1 arises from a reciprocal translocation t(9;22)(q34;q11), between chromosomes 9 and 22, resulting in the formation of the Philadelphia chromosome (Ph) - the first chromosomal abnormality associated with a human malignancy. The BCR::ABL1 fusion gene encodes a constitutively active tyrosine kinase that propels uncontrolled cellular proliferation, enhances cell survival, and leads to leukemogenesis. BCR::ABL1 is the hallmark genetic lesion of Chronic Myeloid Leukemia (CML) and is also reported in a subset of Acute Lymphoblastic Leukemia (ALL) cases. Over the past decades, extensive investigations of BCR::ABL1 have provided a deep understanding of the molecular mechanisms underlying cancer and improved leukemia management. Advances in diagnostic technologies, including cytogenetic analysis, fluorescence in situ hybridization (FISH), and polymerase chain reaction (PCR), have enabled accurate detection and monitoring of the fusion gene. Furthermore, the development of targeted therapies, particularly tyrosine kinase inhibitors, has transformed patient outcomes and established a paradigm for precision medicine in oncology. This review discusses the discovery, molecular basis, biological functions, clinical significance, diagnostic approaches, and therapeutic implications of the BCR::ABL1 fusion gene, emphasising its enduring impact on leukemia research and modern cancer care.