| Budget Amount *help |
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1999: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1998: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1997: ¥900,000 (Direct Cost: ¥900,000)
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| Research Abstract |
Because of recent progress in the molecular biological characterization of B cell response, the normal counterpart of various B cell malignancies can now be investigated. It has been shown that pre-germinal center(GC) B cells, ie, immature sIgM+ B cells and naive mature antigen reactive sIgM+/D+ B cells express Ig V region genes with a germ line sequence in contrast to GC B cells and post-GC B cells that contain mutated V region genes. GC B cells and post-GC B cells can be distinguished from each other, because in GC B cells, the mutation process is usually ongoing, whereas in post-GC B cells this process is switched off. Based on this concept, the IgH genes of various B cell malignancies have been analysed. The analyses of B-CLLs have revealed that the normal counterpart is heterogeneous, ie, originating from sIgM+/D+ naive B cell without somatic mutation and sIgM+/D+ memory B cell with somatic mutations. MALT lymphomas and Burkitt's lymphomas have shown moderate number of somatic mut
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ations and, in few cases, intraclonal diversity. Microdissected tissues to elucidate the relationship between follicular dendritic cell network and tumor cell have been analysed. MALT lymphoma cases demonstrated further intraclonal diversity in follicular colonization lesion, but not in diffuse proliferation lesion without foliicular dendritic cell. However, Burkitt's lymphoma cases showed further intraclonal diversity, irrespective of the presence of follicular dendritic cell network.
Two MCL cases who after a few years developed to the DLBL(anaplastic centrocytic lymphoma) were studied to clarify the mechanism of tumor transformation. In a study of IgH gene, using PCR, the products obtained from each paired sample were the same size, and in one case had an identical sequence to the non-mutated VH gene. There were overexpressions of p53 protein in case 1 and p27 protein in case 2. Although the mechanism of tumor transformation is still poorly understood, the overexpression of p53 or p27 may be linked to a cellular mechanism involved in the development of the variant form of MCL. Less
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