Human pre-B cell acute lymphoblastic leukaemias are associated with a chimaeric gene that is generated from a t(1;19) chromosomal translocation. This fusion joins the regulatory regions of the lymphoid transcription factor gene, E2A, to the C-terminal region, including the homeodomain, of PBX1 (previously called prl). Tow additional human genes (PBX2 and PBX3) with 77-84% identity to PBX1 have been isolated based on sequence similarity. These genes, however, are too closely related to distinguish between recent divergence and conserved essential motifs, if any, outside the homeodomain. Such conserved domains might be revealed by comparing mammalian sequences with those of more evolutionarily distant organisms, such as the expressed sequence tags (ESTs) generated recently in Caenorhabditis elegans.