Reciprocal products of chromosomal translocations in human cancer pathogenesis: key players or innocent bystanders?

Chromosomal translocations are frequently involved in the pathogenesis of leukemias, lymphomas and sarcomas. They can lead to aberrant expression of oncogenes or the generation of chimeric proteins. Classically, one of the products is thought to be oncogenic. For example, in acute promyelocytic leukaemia (APL), reciprocal chromosomal translocations involving the retinoic acid receptor α (RARα) gene lead to the formation of two fusion genes: X–RARα and RARα–X (where X is the alternative RARα fusion partner: PML, PLZF, NPM, NuMA and STAT 5b). The X–RARα fusion protein is indeed oncogenic. However, recent data indicate that the RARα–X product is also critical in determining the biological features of this leukemia. Here, we review the current knowledge on the role of reciprocal products in cancer pathogenesis, and highlight how their expression might impact on the biology of their respective tumour types.