Scheuermann R H, Racila E
Laboratory of Molecular Pathology, University of Texas Southwestern Medical Center, Dallas 75235-9072, USA.
Leuk Lymphoma. 1995 Aug;18(5-6):385-97. doi: 10.3109/10428199509059636.
The CD19 antigen plays an important role in clinical oncology. In normal cells, it is the most ubiquitously expressed protein in the B lymphocyte lineage. CD19 expression is induced at the point of B lineage commitment during the differentiation of the hematopoietic stem cell, and its expression continues through preB and mature B cell differentiation until it is finally down-regulated during terminal differentiation into plasma cells. CD19 expression is maintained in B-lineage cells that have undergone neoplastic transformation, and therefore CD19 is useful in diagnosis of leukemias and lymphomas using monoclonal antibodies (mAbs) and flow cytometry. Interestingly, CD19 is also expressed in a subset of acute myelogenous leukemias (AMLs) indicating the close relationship between the lymphoid and myeloid lineages. Because B lineage leukemias and lymphomas rarely lose CD19 expression, and because it is not expressed in the pluripotent stem cell, it has become the target for a variety of immunotherapeutic agents, including immunotoxins. Treatment of non-Hodgkin's lymphoma (NHL) and acute lymphocytic leukemia (ALL) with anti-CD19 mAbs coupled to biological toxins has proven to be effective in vitro and in animal models, and has shown some promising results in Phase I clinical trials. Recently, the analysis of anti-CD19 effects on lymphoma cell growth has highlighted a novel mechanism of immunotherapy. Engagement of cell surface receptors like CD19 by mAbs can have anti-tumor effects by the activation of signal transduction pathways which control cell cycle progression and programmed cell death (apoptosis).
CD19抗原在临床肿瘤学中发挥着重要作用。在正常细胞中，它是B淋巴细胞谱系中表达最为广泛的蛋白质。在造血干细胞分化过程中，B谱系定向时CD19表达被诱导，其表达贯穿前B细胞和成熟B细胞分化阶段，直至最终在终末分化为浆细胞时下调。CD19表达在发生肿瘤转化的B谱系细胞中得以维持，因此CD19在使用单克隆抗体（mAb）和流式细胞术诊断白血病和淋巴瘤方面很有用处。有趣的是，CD19也在一部分急性髓性白血病（AML）中表达，这表明淋巴谱系和髓系谱系之间存在密切关系。由于B谱系白血病和淋巴瘤很少丧失CD19表达，且它在多能干细胞中不表达，它已成为包括免疫毒素在内的多种免疫治疗药物的靶点。用与生物毒素偶联的抗CD19 mAb治疗非霍奇金淋巴瘤（NHL）和急性淋巴细胞白血病（ALL），已在体外和动物模型中证明有效，并在I期临床试验中显示出一些有前景的结果。最近，对抗CD19对淋巴瘤细胞生长影响的分析突出了一种新的免疫治疗机制。mAb与细胞表面受体如CD19结合，可通过激活控制细胞周期进程和程序性细胞死亡（凋亡）的信号转导途径产生抗肿瘤作用。
