BCR/ABL Oncogene

The BCR/ABL oncogene is the product of the Philadelphia (Ph) chromosome, the derivative (22q) product of a balanced translocation between chromosomes 9 and 22, t(9;22) (q34.1;q11.21). The BCR/ABL gene fusion is the genetic signature of the hematologic malignancy chronic myeloid leukemia (CML). It is also present in a smaller subset of predominantly adult onset B cell-acute lymphoblastic leukemia (B-ALL), where it confers a poor prognosis when treated with standard chemotherapy. Expression of the BCR/ABL fusion protein results in constitutively activated tyrosine phosphorylation of many cellular proteins with subsequent activation of a large number of cell signaling pathways, ultimately leading to neoplastic transformation. CML has been successfully treated with tyrosine kinase inhibitors such as imatinib, although increasing problems with acquired resistance to the inhibitor has led to alternate related drug therapies. Recently, studies have shown high rates of complete remission with the addition of imatinib to treatment protocols for Ph-positive B-ALL.