The goal is analysis of the structure and function of BCL6, a newly identified gene on chromosome 3, band q27, that is associated with a number of common recurring translocations accompanying large cell lymphomas of B-cell type. This endeavor involves isolation of cDNA by multiple rounds of cloning from randomly- and oligo-primed cDNA libraries and comparison of the cDNA sequences with those of known genes in order to gain some insight into function. As soon as an open reading frame is identified, appropriate nucleotide sequences will be cloned into bacterial expression vectors in order to produce a fusion protein, which, when purified, will be injected into rabbits to produce polyclonal antibodies. The antibodies will be used to determine indication of function. Mammalian expression constructs containing BCL6 will be introduced into B-cell lines in an effort to gain some insight into how deregulation of BCL6 affects proliferation, immortalization, and other functions in cells. BCL6 may have a significant function in lymphocytes, since there is evidence of transcriptional activity in T- and B-cell lines. The t(3;14) (q27;q32) and t(3;22) (q27;q11) are the two most common translocations with which this gene is associated. Two independent groups have reported that these recurring translocations are the third most common in non- Hodgkin's lymphomas. Thus, it is likely that aberrant expression of BCL6 has an important role in pathogenesis of certain lymphomas.
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| Baron, Beverly W; Anastasi, John; Montag, Anthony et al. (2004) The human BCL6 transgene promotes the development of lymphomas in the mouse. Proc Natl Acad Sci U S A 101:14198-203 |
| Baron, Beverly W; Anastasi, John; Thirman, Michael J et al. (2002) The human programmed cell death-2 (PDCD2) gene is a target of BCL6 repression: implications for a role of BCL6 in the down-regulation of apoptosis. Proc Natl Acad Sci U S A 99:2860-5 |
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| Baron, B W; Stanger, R R; Hume, E et al. (1995) BCL6 encodes a sequence-specific DNA-binding protein. Genes Chromosomes Cancer 13:221-4 |
