Fusion Genes and Leukemogenesis

Abstract

Many fusion genes have been isolated from genomic breakpoints of chromosome translocations specifically observed in hematopoietic malignancies. Most of the fusion genes involve functionally important key regulatory genes involved in the development of hematopoietic cells, such as transcription factors or protein tyrosine kinases. The loss of functional domain and/or gain of another functional domain from the translocation partner gene often modulate the normal function of a key regulator protein. This abnormally formed fusion protein has the potential to inhibit the differentiation of hematopoietic cells, to promote proliferation, and/or to inhibit apoptotic cell death, finally leading to overt leukemia. The genetic and functional analyses of leukemogenic fusion genes are essential not only to elucidate leukemogenic mechanisms, but also to discover new methods of treatment and ultimately the prevention of leukemia. In this review the current molecular bases of fusion gene formation and current clinical applications are discussed.