| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2000: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1999: ¥2,500,000 (Direct Cost: ¥2,500,000)
|
|---|
| Research Abstract |
BCL6 translocation is one of the most common genetic abnormalities in B-cell tumors, which has been observed in 5-15% of follicular lymphoma and 20-40% of diffuse large B-cell lymphoma (DLBCL). The translocation is unique in that it can involve not only immunoglobulin genes (IGs) but also a number of non-IG loci as partners. We screened >300 cases with B-cell tumors by Southern blot hybridization using a probe for the major translocation cluster of BCL6, and found that 60 cases had rearrangement of the gene. Using long-distance PCR-based approaches, we successfully cloned junctional areas of BCL6 translocations from a total of 58 cases. Nucleotide sequencing and database searches revealed that 30 cases involved IGs as partners : IGH in 22, IGL_κ in 1 and IGLλin 7. In contrast, 23 cases affected non-IG loci, including the H4 histone gene, heat shock protein genes HSP89α and HSP90β, and PIM-1 proto-oncogene, TTF, CIITA, TFRR, IKAROS and α-NAC.We very recently found that the gene for inerleukin-21 receptor (IL-2lR) is the partner of BCL6 in t (3 ; 16)(q27 ; p11) translocation. On der (3) chromosomes, complete sets of the promoters of these partner genes replaced that of BCL6 in the same transcriptional orientation. These results suggest that BCL6 gene affected by the translocation is transcriptionally activated by a variety of stimuli, including cell cycle control, changes in the physical environment, and response to cytokines.
We next studied whether the diverse partner gene can affect the clinical features of DLBCL carrying a particular BCL6 translocation. The results showed that the overall survival of DLBCL patients with non-IG/BCL6 translocation was significantly inferior to that of those with IG/BCL6 translocation (P=0.0440). Thus, it is possible that non-IG partners have influence on the pattern of BCL6 deregulation in a different fashion from IGs, and thereby affect the clinical behavior of DLBCL carrying the corresponding BCL6 translocation.
|
