[Isolation of a novel candidate proto-oncogene involved in human lymphoid neoplasm]

The 14;19 translocation [t(14;19) (q32;q13)] is a recurring chromosomal translocation observed in leukemic cells of chronic lymphocytic leukemia showing prolymphocytic transformation. We have cloned the breakpoint junction of the translocation and identified a new gene, bcl-3, on the chromosome band 19q13 adjacent to the breakpoint. The translocation occurred at the switch region of the alpha constant locus of the immunoglobulin heavy chain gene and the upper stream of the bcl-3 gene, resulting in a head-to-head recombination between the two genes on the 14q+ chromosome. The bcl-3 gene was highly expressed in the leukemic cells carrying the 14;19 translocation. The bcl-3 gene product contained repeat structures found in proteins involved in cell cycle control and cell lineage determination. These results suggest that the bcl-3 is a proto-oncogene that may contribute to the development of leukemias carrying the 14;19 translocation.