Expression of Recombination Activating Gene 1 (RAG-1) in Immature Hematopoietic Neoplasms

免疫球蛋白（IG）或T细胞受体（TCR）基因的单克隆重排检测近年来在造血系统肿瘤的研究中成为热门。这对于证明单克隆性很有用。然而，也已经表明，当包括表型分析在内的其他类型的研究不能揭示谱系或阶段来源时，通过IG或TCR的基因重排分析只能非常罕见地阐明给定造血肿瘤中的衍生谱系或分化阶段。此外，这样的基因分析只能检测重排的产物，并且关于细胞是否能重排IG或TCR基因的问题几乎没有信息。因此，在细胞系或新鲜的人肿瘤细胞中研究了重组酶本身或与重组酶密切相关的分子RAG-1（增殖激活基因-1）的表达。 ...更多信息 RAG-1在未成熟的淋巴样细胞中检测到，但在成熟的淋巴样细胞或霍奇金细胞中未检测到，证明了该测定的可行性。然后，在45例新鲜病例中进行了调查。在B细胞系中，RAG-1在CD 19 +10-20-或CD 19 +10+20-期表达较高，而在CD 19 +10+20+期表达较低。在T细胞系中，RAG-1在胸腺前期（CD 7 +5-2-、CD 7 +5+2-或CD 7 +5+2+3-4-8-）表达缺失或受限，在胸腺期（CD 3 <plus-minus>4+8+）表达强烈，在胸腺晚期（CD 3 4+8-）表达适度。一般来说，TCR δ/γ基因在前胸腺期出现，而TCR β基因则不出现。两个结论性的发现是：[1] RAG-1的表达在肿瘤转化后得以保留，表明造血肿瘤可用于描述正常造血的分化方案。[2]RAG-1对TCR δ/γ基因重排的贡献至少与TCR β基因重排的贡献相比是有限的。后者的发现特别重要，需要进一步的研究，因为小鼠RAG-1基因敲除研究的结果被解释为RAG-1对于TCR δ/γ基因和TCR β基因重排是不可缺少的。少

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. … More 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 TCRbetThe 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