Which gene fusion is characteristic of chronic myeloid leukemia?

• A. BCR-ABL fusion
• B. PML-RARA fusion
• C. JAK2 V617F mutation
• D. BCL-2 translocation

Answer: (A)

Chronic myeloid leukemia is driven by a reciprocal translocation that creates the BCR-ABL fusion gene, producing a constitutively active tyrosine kinase. This abnormal signaling drives unchecked myeloid proliferation and defines the disease, with the Philadelphia chromosome (t(9;22)) detectable by cytogenetics or FISH and by the BCR-ABL transcript. This fusion is a primary diagnostic and therapeutic target, with tyrosine kinase inhibitors like imatinib changing the disease’s course. Other options reflect fusions or mutations seen in different conditions: the PML-RARA fusion from t(15;17) is classic for acute promyelocytic leukemia, not CML; JAK2 V617F is typical of certain myeloproliferative neoplasms; and a BCL-2 translocation (t(14;18)) is associated with follicular lymphoma. Thus, the characteristic gene fusion in chronic myeloid leukemia is BCR-ABL.