Foon K A, Todd R F
Blood. 1986 Jul;68(1):1-31.
Important insights into leukocyte differentiation and the cellular origins of leukemia and lymphoma have been gained through the use of monoclonal antibodies that define cell surface antigens and molecular probes that identify immunoglobulin and T cell receptor genes. Results of these studies have been combined with markers such as surface membrane and cytoplasmic immunoglobulin on B lymphocytes, sheep erythrocyte receptors on T lymphocytes, and cytochemical stains. Using all of the above markers, it is now clear that acute lymphoblastic leukemia (ALL) is heterogeneous. Furthermore, monoclonal antibodies that identify B cells, such as the anti-B1 and anti-B4 antibodies in combination with studies of immunoglobulin gene rearrangement, have demonstrated that virtually all cases of non-T-ALL are malignancies of B cell origin. At least six distinct subgroups of non-T-ALL can now be identified. T-ALL is subdivided by the anti-Leu-9, anti-Leu-1, and antibodies that separate T lymphocyte subsets into three primary subgroups. Monoclonal antibodies are also useful in the subclassification of non-Hodgkin's lymphoma, and certain distinct markers can be correlated with morphologic classification. The cellular origin of the malignant Reed-Sternberg cell in Hodgkin's disease remains uncertain. A substantial number of investigators favor a myelocyte/macrophage origin based on cytochemical staining; however, consistent reactivity with antimonocyte reagents has not been demonstrated. Although monoclonal antibodies are useful in distinguishing acute myeloid from acute lymphoid leukemias, they have less certain utility in the subclassification of acute myelogenous leukemia (AML). Attempts to subclassify AML by differentiation-associated antigens rather than by the French-American-British (FAB) classification are underway in order to document the potential prognostic utility of surface markers. Therapeutic trials using monoclonal antibodies in leukemia and lymphoma have been reported. Intravenous (IV) infusion of unlabeled antibodies is the most widely used method; transient responses have been demonstrated. Antibodies conjugated to radionuclides have been quite successful in localizing tumors of less than 1 cm in some studies. Therapy trials with antibodies conjugated to isotopes, toxins, and drugs are currently planned. Purging of autologous bone marrow with monoclonal antibodies and complement in vitro has been used in ALL and non-Hodgkin's lymphoma; preliminary data suggest that this approach may be an effective therapy and may circumvent many of the obstacles and toxicities associated with in vivo monoclonal antibody infusion.
通过使用定义细胞表面抗原的单克隆抗体和识别免疫球蛋白及T细胞受体基因的分子探针，人们对白细胞分化以及白血病和淋巴瘤的细胞起源有了重要认识。这些研究结果已与诸如B淋巴细胞上的表面膜和细胞质免疫球蛋白、T淋巴细胞上的绵羊红细胞受体以及细胞化学染色等标志物相结合。利用上述所有标志物，现已明确急性淋巴细胞白血病（ALL）具有异质性。此外，识别B细胞的单克隆抗体，如抗B1和抗B4抗体，结合免疫球蛋白基因重排研究，已证明几乎所有非T-ALL病例均为B细胞起源的恶性肿瘤。目前至少可识别出六个不同的非T-ALL亚组。T-ALL可通过抗Leu-9、抗Leu-1以及将T淋巴细胞亚群分开的抗体细分为三个主要亚组。单克隆抗体在非霍奇金淋巴瘤的亚分类中也很有用，某些独特的标志物可与形态学分类相关联。霍奇金病中恶性里德-斯腾伯格细胞的细胞起源仍不确定。大量研究人员基于细胞化学染色支持其起源于髓细胞/巨噬细胞；然而，尚未证明其与抗单核细胞试剂有一致的反应性。尽管单克隆抗体在区分急性髓细胞白血病和急性淋巴细胞白血病方面很有用，但它们在急性髓细胞白血病（AML）的亚分类中的效用不太确定。目前正在尝试通过分化相关抗原而非法国-美国-英国（FAB）分类对AML进行亚分类，以证明表面标志物的潜在预后效用。已有关于在白血病和淋巴瘤中使用单克隆抗体的治疗试验的报道。静脉内（IV）输注未标记抗体是最广泛使用的方法；已证明有短暂反应。在一些研究中，与放射性核素偶联的抗体在定位小于1厘米的肿瘤方面相当成功。目前正在计划进行与同位素、毒素和药物偶联抗体的治疗试验。在ALL和非霍奇金淋巴瘤中已使用单克隆抗体和补体在体外清除自体骨髓；初步数据表明这种方法可能是一种有效的治疗方法，并且可能规避与体内单克隆抗体输注相关的许多障碍和毒性。
