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

近年来，检测免疫球蛋白(Ig)或T细胞受体(TCR)基因的单克隆性重排已成为血液系统肿瘤研究的热点。这对于证明单克隆性很有用。然而，也有研究表明，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派生时，只有极少数情况下，通过Ig或TCR的基因重排分析才能阐明特定血液系统肿瘤的派生谱系或分化阶段。此外，这种基因分析只能检测到重排的结果，对于细胞是否可以重排Ig或TCR基因的问题提供的信息很少。因此，我们研究了重组酶本身或与重组酶密切相关的分子RAG-1(重组激活基因-1)在细胞系或新鲜人肿瘤细胞中的表达。…在未成熟的淋巴样细胞中检测到更多的RAG-1，而在成熟的淋巴样细胞或霍奇金细胞中检测不到RAG-1，证明了该方法的可行性。然后，对45例新鲜病例进行调查。B系CD19+10-20-或CD19+10+20-期RAG-1表达较高，CD19+10+20+期RAG-1表达较低。在T细胞系中，RAG-1在胸腺前期(CD7+5-2-、CD7+5+2-或CD7+5+2+3-4-8-)缺失或表达受限，在胸腺期(CD3+lt；正负+Gt；4+8+)表达强烈，在胸腺晚期(CD3+4+8-)表达较弱。TCRDelta/Gamma基因一般在胸腺前期重排，而TCRbeta基因则不重排。[1]肿瘤转化后RAG-1的表达保持不变，提示造血肿瘤可用于勾画正常造血的分化机制。[2]与TCRbeta基因重排相比，RAG-1对TCRDelta/Gamma基因重排的贡献至少是有限的。后一发现尤其重要，需要进一步研究，因为RAG-1基因敲除小鼠的研究结果表明，RAG-1对TCRDelta/Gamma基因重排和TCRbeta基因重排都是不可或缺的。较少

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