What gene fusion is most commonly associated with Chronic Myeloid Leukemia (CML)?

The gene fusion most commonly associated with Chronic Myeloid Leukemia (CML) is BCR-ABL1. This fusion results from a translocation between chromosomes 9 and 22, specifically t(9;22)(q34;q11), which is known as the Philadelphia chromosome. The BCR-ABL1 protein that is produced by this fusion has constitutive tyrosine kinase activity, which leads to the proliferation of myeloid cells and decreased apoptosis. This mechanism is critical for the pathogenesis of CML and significantly contributes to the characteristics of the disease, including the presence of an elevated white blood cell count and splenomegaly.

In contrast, the other gene fusions mentioned are associated with different types of malignancies. MYC-IGH is often linked to Burkitt lymphoma, PML-RARA is associated with acute promyelocytic leukemia (APL), and BCL2-IGH is related to follicular lymphoma. These gene fusions serve as important diagnostic markers and therapeutic targets in their respective diseases but do not play a role in the pathogenesis of CML. Understanding the specific gene fusions related to different hematologic malignancies is essential for their accurate diagnosis and treatment.