B cell origin of non-T cell acute lymphoblastic leukemia. A model for discrete stages of neoplastic and normal pre-B cell differentiation.
B cell origin of non-T cell acute lymphoblastic leukemia. A model for discrete stages of neoplastic and normal pre-B cell differentiation.
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非T细胞急性淋巴细胞白血病的B细胞起源。
DOI：
10.1172/jci111428
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发表时间：
1984
期刊：
影响因子：
--
通讯作者：
Sallan,SE
中科院分区：
文献类型：
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作者：
Nadler,LM;Korsmeyer,SJ;Anderson,KC;Boyd,AW;Slaughenhoupt,B;Park,E;Jensen,J;Coral,F;Mayer,RJ;Sallan,SE
应用流式细胞仪检测138例非T细胞急性淋巴细胞白血病(Non-T cell ALL)患者肿瘤细胞表面B细胞相关抗原和限制性抗原的表达。这些患者的肿瘤细胞可分为四个亚型之一：单独的人类白细胞抗原DR相关Ia样抗原(Ia)(4%，I期)；IaB4(14%，II期)；IaB4CALLA(33%，III期)；以及IaB4CALLAB1(49%，IV期)。B细胞限制性抗原(B4和B1)的表达和Ig重链基因的重排为II、III和IV期肿瘤的B细胞谱系提供了强有力的证据。仅Ia群体的血统仍不清楚。在所有检测的非T细胞ALL中，约95%的细胞表达B4抗原，鉴于T细胞和髓系肿瘤不表达B4抗原，B4抗原似乎是界定B细胞系的特殊标志。在正常胎儿和成人骨髓中，Ia、IaB4、IaB4CALLA和IaB4CALLAB1阳性细胞可以通过双重荧光分析很容易地被识别出来，这为这些白血病前B细胞表型代表正常前B细胞分化阶段的观点提供了关键支持。有趣的是，IaB4+细胞在胎儿骨髓中比在成人骨髓中更常见，而在成人骨髓中发现的主要细胞表达IaB4CALLAB1表型。这些数据表明，导致白血病的事件可能是随机的，因为主要的前B细胞白血病表型似乎与这些造血器官中存在的正常前B细胞表型相对应。我们的观察提供了成人ALL和儿童ALL之间的额外区别，因为这些研究表明，在2岁以下的儿童中，大多数非T细胞ALL是II期表型，而成年人的大多数非T细胞ALL是IV期表型。最后，值得注意的是，本研究表明，对白血病B细胞表型及其正常对照的分析可以为研究和有序定义人类前B细胞分化阶段提供一种机制。
The expression of B cell associated and restricted antigens on tumor cells isolated from 138 patients with non-T cell acute lymphoblastic leukemia (non-T cell ALL) was investigated by flow cytometric analysis by means of a panel of monoclonal antibodies. Tumor cells from these patients could be assigned to one of four subgroups: human leukocyte antigen-DR-related Ia-like antigens (Ia) alone (4%, stage I); IaB4 (14%, stage II); IaB4CALLA (33%, stage III); and IaB4CALLAB1 (49%, stage IV). The expression of B cell-restricted antigens (B4 and B1) and rearrangements of Ig heavy chain genes provided strong evidence for the B cell lineage of stages II, III, and IV tumors. The lineage of the Ia alone group is still unknown. The B4 antigen was expressed on approximately 95% of all non-T cell ALLs tested, and given its absence on T cell and myeloid tumors, it appears to be an exceptional marker to define cells of B lineage. The demonstration that Ia alone, IaB4, IaB4CALLA, and IaB4CALLAB1 positive cells can be readily identified by dual fluorescence analysis in normal fetal and adult bone marrow provided critical support for the view that these leukemic pre-B cell phenotypes were representative of the stages of normal pre-B cell differentiation. It was interesting that the IaB4+ cell was more frequently identified in fetal bone marrow than in adult marrow, whereas the predominant cell found in adult marrow expressed the IaB4CALLAB1 phenotype. These data suggest that the leukemogenic event may be random, since the predominant pre-B cell leukemic phenotype appears to correspond to the normal pre-B cell phenotype present in these hematopoietic organs. Our observations provide an additional distinction between adult and childhood ALL, since these studies show that most non-T cell ALLs seen in children less than 2 yr old are of stage II phenotype, whereas the majority of non-T ALLs in adults are of stage IV phenotype. Finally, it should be noted that the present study suggests that the analysis of leukemic B cell phenotypes and their normal counterparts can provide a mechanism for the investigation and orderly definition of stages of pre-B cell differentiation in man.