| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2004: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2003: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2002: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Research Abstract |
Recently, we established an ELISA technique for measuring nm23-H1 protein in serum, and found that the serum nm23-H1 level is a potential prognostic factor for patients with non-Hodgkin's lymphoma. We used immunohistochemistry to examine the expression of nm23-H1 by the lymphoma cells in patients with diffuse large B-cell lymphoma (DLBCL) or peripheral T-cell lymphoma (PTCL). By analyzing a consecutive series of 172 untreated DLBCL patients, 100 (58.1%) were strongly positive. The cytoplasmic nm23 expression in lymphoma cells correlated significantly with the serum nm23-H1 level. There was a significant correlation between patients with cytoplasmic nm23-positive lymphoma and those with PS 2-4, stage III/IV, bulky mass, B symptoms, elevated serum level of sIL-2R, and elevated serum level of CRP. Overall and progression-free survival rates were significantly lower in patients with nm23-H1-positive lymphomas than in those with nm23-H1-negative lymphomas. Similar difference was seen betwee
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n patients with high and low serum levels of nm23-H1. Thus, the correlation between presence or absence of cytoplasmic nm23-H1 expression and serum nm23-H1 levels suggests that serum nm23-H1 is produced directly by lymphoma cells. Expression of nm23-H1, TIA-1 or granzyme B was examined by immunohistochemistry in 137 previously untreated patients with the lymphoma. The relationship between the results and clinical outcome was examined in 81 patients with angioimmunoblastic T-cell lymphoma, anaplastic large cell lymphoma, or peripheral T-cell lymphoma-unspecified. It was found that nm23-H1 was produced by the neoplastic cells of some of the lymphoma and the expression rates of nm-23-H1, TIA-1, and granzyme B were 36.5%, 78.8%, and 32.8%, respectively. nm23-H1-positive or TIA-1-positive group had significantly shorter overall and disease-free survivals. Furthermore, a multivariate analysis confirmed the nm23-H1 expression to be an independent prognostic factor.
Because of nm23-HI production by lymphoma cells, we expect to see the development of new treatments targeting nm23 overexpression. Furthermore, the nm23-H1 protein can be an important prognostic factor in the above types of lymphoma. Less
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