Recurrent chromosomal translocations and fusion genes in leukemia-lymphoma cell lines

Abstract

The occurrence of defined chromosomal translocations in specific subtypes of leukemia and lymphoma strongly suggests that these structural alterations play an important role in the process of tumorigenesis. Translocations may activate nearby cellular genes involved in the control of proliferation or differentiation. One mechanism by which genes become activated or overexpressed is by their juxtaposition with the genes coding for the lymphoid antigen receptors (immunoglobulins or T cell receptors). The majority of the translocated genes appear to encode transcription factors, the expression of which might become deregulated due to the influence of regulatory elements in the antigen receptor loci. A second general type of chromosomal translocation by which proto-oncogenes can be activated results in the synthesis of fusion genes. Here, chimera proteins containing portions of two different proteins are generated following exon-exon juxtaposition of two genes lying at the sites of translocation. The list of such tumor-associated fusion genes generated by specific translocations has greatly increased over the last years. A wide variety of leukemia-lymphoma cell lines have been established to act both as genetic resources and as model systems for the different disease types and stages providing an inexhaustible source of replicate material. For many translocations, DNA spanning the breakpoint was isolated by using cell lines carrying the particular abnormality. The cloning of the genes disrupted by the translocations has led to the availability of probes useful for diagnosis and monitoring of patients, eg with polymerase chain reaction (PCR) assays. Here, we review the cytogenetic and molecular data of chromosomal aberrations associated with leukemia-lymphoma and indicate a panel of human cell lines carrying such specific chromosomal abnormalities.