Harris N L, Stein H, Coupland S E, Hummel M, Favera R D, Pasqualucci L, Chan W C
Department of Pathology, Massachusetts General Hospital, Boston, MA 02114, USA.
Hematology Am Soc Hematol Educ Program. 2001:194-220. doi: 10.1182/asheducation-2001.1.194.
Recent years have brought an explosion of new diagnostic tools to the pathology of lymphomas, which have permitted more precise disease definition and recognition of factors that can predict prognosis and response to treatment. These new methods exploit both the biological features of normal lymphocytes as they progress through differentiation pathways and the genetic abnormalities that characterize malignant transformation. These features can be assessed in individual tumors with techniques that detect proteins (immunophenotyping), messenger RNA (in-situ hybridization), or changes in DNA [Southern blot, PCR, fluorescence in-situ hybridization (FISH), and gene sequencing]. Recently, the novel technology of "gene chips" or DNA microarrays has greatly enhanced the efficiency of analyzing expression of many genes simultaneously at the RNA level. Understanding the relationship of lymphoid neoplasms to their normal counterparts and the genetic events that lead to malignant transformation in lymphoid cells are essential for physicians caring for patients with lymphoma, since these are the basis of modern classification, diagnosis, and prognosis prediction. Although microarray technology is not ready for prime time in the daily diagnosis of lymphoma, practitioners should understand its potential and limitations. The vast majority of lymphoid neoplasms worldwide are derived from B lymphocytes at various stages of differentiation. The review by Harald Stein and colleagues present the events of normal B-cell differentiation that are relevant to understanding the biology of B-cell neoplasia. These include antigen receptor [immunoglobulin (Ig)] gene rearrangement, somatic mutations of the Ig variable region genes, receptor editing, Ig heavy chain class switch, and differential expression of a variety of adhesion molecules and receptor proteins as the cell progresses from a precursor B cell to a mature plasma cell. Most lymphoid neoplasms have genetic abnormalities, many of which appear to occur during the gene rearrangements and mutations that characterize normal B-cell differentiation. Dr. Riccardo Dalla Favera reviews the mechanisms of these translocations and other abnormalities, and their consequences for lymphocyte biology. The association of specific abnormalities with individual lymphomas is reviewed. Dr. Wing C. Chan reviews the technology and applications of DNA microarray analysis, its promises and pitfalls, and what it has already told us about the biology of lymphomas. Finally, what does this all mean? The applications, both current and future, of these discoveries to the diagnosis and treatment of patients with lymphoma are discussed by Dr. Nancy Lee Harris.
近年来，淋巴瘤病理学领域涌现出大量新的诊断工具，这些工具使疾病定义更加精确，有助于识别能够预测预后和治疗反应的因素。这些新方法既利用了正常淋巴细胞在分化过程中的生物学特性，也利用了恶性转化所特有的基因异常。通过检测蛋白质（免疫表型分析）、信使核糖核酸（原位杂交）或DNA变化（Southern印迹法、聚合酶链反应、荧光原位杂交和基因测序）的技术，可以在单个肿瘤中评估这些特征。最近，“基因芯片”或DNA微阵列这项新技术极大地提高了在RNA水平上同时分析多个基因表达的效率。对于治疗淋巴瘤患者的医生来说，了解淋巴样肿瘤与其正常对应物的关系以及导致淋巴样细胞恶性转化的基因事件至关重要，因为这些是现代分类、诊断和预后预测的基础。虽然微阵列技术在淋巴瘤的日常诊断中尚未成熟，但从业者应该了解其潜力和局限性。全球绝大多数淋巴样肿瘤源自不同分化阶段的B淋巴细胞。哈拉尔德·施泰因及其同事的综述介绍了与理解B细胞肿瘤生物学相关的正常B细胞分化事件。这些事件包括抗原受体[免疫球蛋白（Ig）]基因重排、Ig可变区基因的体细胞突变、受体编辑、Ig重链类别转换，以及随着细胞从前体B细胞发育为成熟浆细胞，各种黏附分子和受体蛋白的差异表达。大多数淋巴样肿瘤存在基因异常，其中许多异常似乎发生在正常B细胞分化所特有的基因重排和突变过程中。里卡尔多·达拉·法韦拉博士综述了这些易位和其他异常的机制，以及它们对淋巴细胞生物学的影响。文中还综述了特定异常与个体淋巴瘤的关联。Wing C. Chan博士综述了DNA微阵列分析的技术和应用、其前景与陷阱，以及它已经告诉我们的关于淋巴瘤生物学的信息。最后，这一切意味着什么呢？南希·李·哈里斯博士讨论了这些发现目前及未来在淋巴瘤患者诊断和治疗中的应用。
