HETEROGENEITY OF BREAKPOINTS AT THE TRANSCRIPTIONAL COACTIVATOR GENE,BOB-1, IN LYMPHOPROLIFERATIVE DISEASE

Chromosome 11q23 is frequently a site of chromosomal translocation in both acute leukemias and chronic lymphoproliferative disorders. In the former, an 8 kb region within the MLL gene is consistently involved, whereas in the latter breakpoints appear to be heterogeneous. In a 8 c ell acute leukemia cell line with t(14;18)(q32.3;q21.3) we have previo usly demonstrated a reciprocal translocation between the LAZ3/BCL6 gen e at 3q27 and the 8 cell specific transcriptional coactivator gene BOB -1 at 11q23.1, implicating BOB-1 as a potential proto-oncogene. To con firm the chromosomal localization of BOB-1 we have mapped it by FISH t o 11q23.1. it lay immediately telomeric of the ATM gene. We have also investigated the frequency of BOB-1 rearrangements in a panel of 32 ce ll lines and 71 patient samples. In one case of T cell prolymphocytic leukemia - a disease where 11q23 abnormalities are observed - a chromo somal rearrangement was identified 3.3-0.9 kb centromeric of the 3' en d of the gene. Thus, there is a heterogeneity of breakpoints associate d with BOB-1 while the frequency of the gene's involvement in lymphopr oliferative diseases is low.