Fusion Genes in Myeloid Malignancies

Fusion genes arise from gross chromosomal rearrangements and have been closely linked to oncogenesis. In myeloid malignancies, fusion genes play an integral role in the establishment of diagnosis and prognostication. In the clinical management of patients with acute myeloid leukemia, fusion genes are deeply incorporated in risk stratification criteria to guide the choice of therapy. As a result of their intrinsic ability to define specific disease entities, oncogenic fusion genes also have immense potential to be developed as therapeutic targets and disease biomarkers. In the current era of genomic medicine, breakthroughs in innovation of sequencing techniques have led to a rise in the detection of novel fusion genes, and the concept of standard-of-care diagnostics continues to evolve in this field. In this review, we outline the molecular basis, mechanisms of action and clinical impact of fusion genes. We also discuss the pros and cons of available methodologies that can be used to detect fusion genes. To contextualize the challenges encountered in clinical practice pertaining to the diagnostic workup and management of myeloid malignancies with fusion genes, we share our experience and insights in the form of three clinical case studies.