Analysis of immunoglobulin, T cell receptor and cytokine genes in hematologic neoplasms

免疫球蛋白(Ig)或T细胞受体(TCR)链基因在所有表型不明的细胞淋巴瘤中均有重排，提示这些基因重排是确定细胞谱系和克隆性的有力工具。TCR链基因重排在T细胞和未成熟B细胞肿瘤中常见，在成熟B细胞肿瘤中未见。此外，在与TCR链基因重排相关的未成熟B细胞白血病中也发现了TCR链基因重排。这些结果表明，对Ig和TCR基因的分析为鉴定淋巴细胞分化的正常阶段提供了一种潜在的工具。成人T细胞白血病(ATL)细胞表面的TCR和CD3抗原密度较低，提示CD3-TCR复合体与抗原的相互作用诱导了它们的调节。TCR链不同病变的氨基酸序列之间没有明显的同源性，ATL细胞TCR和链基因重排模式的图谱是异质性的。然而，CD3-TCR复合体的表达缺陷与新鲜细胞和培养细胞的基因型相同有明显的相关性，提示CD3-TCR复合体的表达缺陷可能在ATL的发生发展中起关键作用。另一方面，在一例髓系白血病患者的细胞中，观察到IL-1的显著增殖，并被抗IL-1抗体抑制。培养上清液中含有IL-1活性，Northern印迹分析检测到细胞内IL-1mRNA的表达，提示IL-1的自分泌参与了部分髓系白血病细胞的增殖。因此，对Ig、TCR和细胞因子基因的分析是对血液肿瘤进行分类和定性的有力工具。

Rearrangements of immunoglobulin (Ig) or T cell receptor (TCR) chain gene were observed in all of lymph node cells from phenotypically undetermined cell lymphoma, suggesting that demonstration of these gene rearrangements is a powerful tool to determine cell lineage and clonality. TCR chain gene rearrangement was frequently found in both T cell and immature B cell neoplasms and was not observed in mature B cell neoplasms. Furthermore, rearrangement of TCR chain gene was also found in immature B cell leukemias associated with TCR chain gene rearrangement. These results indicate that an analysis of Ig and TCR gene provides a potential tool to identify the normal stages of lymphocyte differentiation. The density of TCR and CD3 antigens on adult T cell leukemia (ATL) cells are low, indicating that interactions of atnigents to CD3-TCR complex induce their modulation. No significant homologies were noted among the deduced amino acid sequences of variable lesions of TCR chain, and the plofiles of rearrangement patterns of TCR and chain gene in ATL cells were heterogenous. However, there were apparent associations between a defect of expression of CD3-TCR complex and identical genotypes of fresh and cultured cells, suggesting that the defect of expression of CD3-TCR complex may play a key role for development of ATL. On the other hand, a significant proliferation by IL-1, which were inhibited by anti-IL-1 antibody, was observed in cells from a patient with myeloid leukemia. Culture supernatants of these leukemic cells contained IL-1 activity and northern blot analysis detected intracellular IL-1 mRNA, indicating that autocrine secretion of IL-1 was involved in proliferation of some myeloid leukemic cells. Thus, an analysis of Ig, TCR and cytokine genes is a powerful tool to classify and characterize hematologic neoplasms.