| Budget Amount *help |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1994: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1993: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Research Abstract |
The detection of monoclonal rearrangements of the genes of immunoglobulins (Ig) or T-cell receptors (TCR) has recently become popular in the studies of hematopoietic neoplasms. It is useful for proving monoclonality. However, it has also been shown that the derived lineage or stage of differentiation in a given hematopoietic neoplasm can be clarified only very rarely by the gene rearrangement analysis of Ig or TCR,when other types of studies including phenotypic analysis fail to reveal the lineage- or stage-derivation. Furthermore, such gene analysis can detect only the resultant products of the rearrangement, and is little informative regarding the question if the cells can rearrange the Ig or TCR genes. Thus, the expression of RAG-1 (Recombination Activating Gene-1) , a recombinase itself or a molecule closely related to the recombinase, was investigated in cell-line or fresh human neoplastic cells.
First, the expression of RAG-1 was investigated in 31 human hematopoietic cell-lines.
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RAG-1 was detected in immature lymphoid cells, but not in mature lymphoid or Hodgkin cells, proving the feasibility of the assay. Then, the investigation was performed in 45 fresh cases. In B-lineage, RAG-1 was high in CD19+10-20- or CD19+10+20-, but low in CD19+10+20+ stage. In T-lineage, the RAG-1 expression was absent or limited in the pro-thymic stage (CD7+5-2-, CD7+5+2- or CD7+5+2+3-4-8-) , intense in the thymic stage (CD3<plus-minus>4+8+) and modest in the late thymic stage(CD3+4+8-). Generally, TCRdelta/gamma gene is rearanged in the pro-thymic stage, but TCRbeta gene not. Two conclusive findings are : [1] The expression of RAG-1 is preserved after neoplastic transformation, indicating the usefullness of the hematopoietic neoplasms for delineating the differentiation scheme of normal hematopiesis. [2] The contribution of RAG-1 to the gene rearrangement of TCRdelta/gamma is at least limited compared with that to the gene rearangement of TCRbet
The latter finding is particularly important, requiring further investigations, since the results of the RAG-1 gene-knock-out studies in mouse are interpreted to indicate that RAG-1 is indispensable for rarranging TCRdelta/gamma gene as well as TCRbeta gene. Less
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