| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2001: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2000: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1999: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Research Abstract |
EB virus associated peripheral T cell lymphoma (EBV-PTCL) is a fatal disorder of monoclonally proliferated EB virus infected T cells. Clinical characteristics of EBV-PTCL consist of persistent high fever, pancytopenia, liver dysfunction, coagulopathy, and hemophagocytic syndrome. Lymphoma cells of EBV-PTCL are functionally active in cytokine production and cytotoxicity, which may be affected by the infected EBV. LMP1 protein, one of the most important proteins of EB virus, has oncogenic activity, and has a potential to up-regulate KF-κB activity, which is a potent cytokine production regulator in T cells. Therefore, it was interesting to elucidate the role of LMP1 in EBV-PTCL.
In the present study, we have analyzed LMP1 gene obtained from EBV-PTCL patients, and found that LMP1 from EBV-PTCL shared common features of 8 amino acids replacement (Q189P, S192T, G212S, S309N, Q322N/H/I, Q334R, L338S, S366T) and 10 amino acids deletion. That is EB virus possessing this type of mutant LMP1 may play a role in pathogenesis of EBV-PTCL. Further, as for potential to up-regulation of NF-κB activity, mutant LMP1 has significantly strong activity. Therefore, it is conceivable that EB virus possessing mutant LMP1 transformed T cells, and lead massive cytokine production in EBV-PTCL via its strong NF-κB activation.
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