AbstractEukaryotic cells contain a family of genes termed cellular oncogenes or proto-oncogenes thought to regulate normal cell growth and development. In some abnormal circumstances, such as following transduction by retroviruses, activation of these genes causes leukemias in animals. Possible mechanisms of activation of cellular oncogenes include: point mutation, deletion, or insertion; amplification; activation by internal rearrangement, chromosomal translocation, or promoter insertion; recom-binatorial events resulting in the formation of novel chimeric genes; among others. In this review, we consider data implicating activation of cellular oncogenes in the pathogenesis of leukemia in humans. We discuss possible mechanisms whereby oncogene activation may induce leukemias, as well as potential diagnostic and therapeutic implications.