Antigen receptor genes as molecular markers of lymphoid neoplasms.
Antigen receptor genes as molecular markers of lymphoid neoplasms.
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抗原受体基因作为淋巴肿瘤的分子标记。
DOI：
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发表时间：
1987
影响因子：
15.9
通讯作者：
S. Korsmeyer
中科院分区：
文献类型：
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作者：
S. Korsmeyer
人类淋巴肿瘤的分子分析正在显著改变我们对其发病机制和分类的概念。在重组DNA时代之前，代表B或T细胞成熟阶段的细胞表面抗原的研究取得了重大进展（1）。尽管产生了许多针对B和T细胞抗原的抗体，但仍无法对某些淋巴肿瘤的细胞类型进行分类。这种不充分常常反映了淋巴瘤组织中有大量非肿瘤细胞的混合。这些细胞不能被区分，因为几乎所有的谱系相关标记都存在于正常和恶性细胞上。在其他情况下，白血病代表谱系限制性抗原表达之前的发育阶段。通常，甚至不可能确定淋巴肿瘤是否是克隆起源的。在B或T细胞中组装抗原特异性受体基因的DNA重排提供了克服许多这些限制的必要工具。免疫球蛋白（IG）和T细胞受体（TCR）1基因在其生殖系或胚胎状态下由多个分离的基因亚段组成。在淋巴发育期间，DNA重组过程组装B细胞中的IG基因或T细胞中的TCR基因的组分（2-4）。我们对这些基因的了解，包括它们的DNA重排顺序、重组机制、体细胞突变、RNA剪接和转录调控等，大多来自已建立的淋巴肿瘤。作为回报，这些对基础生物学的贡献通过解决有关白血病和淋巴瘤的谱系承诺、克隆性、发育阶段和发病机制的不确定性而获得了回报。具体而言，IG和TCR基因重排产生每个细胞特有的DNA水平标记。这种敏感和特异的分子指纹能够鉴定B或T细胞的克隆扩增。此外，IG和TCR基因重排的发育层次发生在早期B和T细胞成熟，提供了新的手段分类肿瘤。最重要的是，已经发现了Ig和TCR基因座的意外重排，这直接导致了肿瘤的发生。
Molecular analysis of human lymphoid neoplasms is markedly altering our concepts of their pathogenesis and classification. Before the era of recombinant DNA, major advances were provided by the investigation of cell surface antigens representing maturational stages of B or T cells (1). Despite the generation ofmany antibodies to B and T cell antigens, it was still impossible to classify the cellular type of some lymphoid neoplasms. This inadequacy frequently reflected the admixture of large numbers of nonneoplastic cells within lymphomatous tissue. Such cells could not be distinguished inasmuch as virtually all the lineageassociated markers were present on normal as well as malignant cells. In other instances, leukemias represented stages of development prior to the expression of lineage-restricted antigens. Frequently, it was even impossible to determine whether a lymphoid neoplasm was of clonal origin. The rearrangements of DNA which assemble the antigenspecific receptor genes in B or T cells provide the necessary tools to overcome many of these limitations. The immunoglobulin (Ig) and T cell receptor (TCR)1 genes are composed of multiple, separated gene subsegments within their germline or embryonic state. During lymphoid development a DNA recombination process assembles the components of Ig genes in B cells or TCR genes in T cells (2-4). Most of our knowledge concerning these genes including their ordered sequence ofDNA rearrangements, mechanisms of recombination, somatic mutation, alternative RNA splicing, and transcriptional regulation was gleaned from established lymphoid neoplasms. In return, these contributions to basic biology have paid dividends by resolving uncertainties concerning the lineage commitment, clonality, stage of development, and pathogenesis of leukemias and lymphomas. Specifically, Ig and TCR gene rearrangements create DNA-level markers unique to each individual cell. This sensitive and specific molecular fingerprint is capable of identifying a clonal expansion of B or T cells. Moreover, a developmental hierarchy for both Ig and TCR gene rearrangements occurs during early B and T cell maturation, providing new means ofcategorizing neoplasms. Most importantly, unanticipated rearrangements ofIg and TCR loci have been discovered which directly contribute to the ma-