Shin Y K, Choi E Y, Kim S H, Chung J, Chung D H, Park W S, Jung K C, Kim H S, Park S, Kim H J, Park M H, Min C K, Kim C C, Park S H
Department of Pathology, Seoul National University College of Medicine, 28 Yongon-dong, Chongno-gu, Seoul 110-799, Korea.
Am J Pathol. 2001 Apr;158(4):1473-80. doi: 10.1016/s0002-9440(10)64098-9.
The identification of immunophenotypic markers with restricted expression has long been a critical issue in diagnostic and therapeutic advances for acute leukemias. We previously developed a monoclonal antibody against a new thymocyte surface antigen, JL1, and showed that JL1 is expressed in the majority of acute leukemia cases. In this study, using multiparameter flow cytometric analyses, we found that JL1 was uniquely expressed in subpopulations of normal bone marrow (BM) cells, implying the association of JL1 with the differentiation and maturation process. Although CD34(+) CD10(+) lymphoid precursors and some of maturing myeloid cells express JL1, neither CD34(+) CD38(-/lo) nor CD34(+) AC133(+) noncommitted pluripotent stem cells do. As for the myeloid precursors, CD34(+) CD33(+) cells do not express JL1. During lymphopoiesis, JL1 on the earliest lymphoid precursors disappear in the CD20(+) sIgM(+) stage of B-cell development or after CD1a down-regulation in thymocytes. Despite the highly restricted expression of JL1 in normal BM cells, most of the leukemias express JL1 irrespective of their immunophenotypes. These results indicate that JL1 is not only a novel differentiation antigen of hematopoietic cells, but also a leukemia-associated antigen. Therefore, we suggest that JL1 be a candidate molecule in acute leukemia for the diagnosis and immunotherapy that spares the normal BM stem cells.
鉴定具有受限表达的免疫表型标志物长期以来一直是急性白血病诊断和治疗进展中的关键问题。我们之前开发了一种针对新的胸腺细胞表面抗原JL1的单克隆抗体,并表明JL1在大多数急性白血病病例中表达。在本研究中,通过多参数流式细胞术分析,我们发现JL1在正常骨髓(BM)细胞亚群中独特表达,这意味着JL1与分化和成熟过程相关。虽然CD34(+) CD10(+)淋巴样前体细胞和一些成熟髓样细胞表达JL1,但CD34(+) CD38(-/lo)细胞或CD34(+) AC133(+)未定向多能干细胞均不表达。至于髓样前体细胞,CD34(+) CD33(+)细胞不表达JL1。在淋巴细胞生成过程中,最早淋巴样前体细胞上的JL1在B细胞发育的CD20(+) sIgM(+)阶段或胸腺细胞中CD1a下调后消失。尽管JL1在正常BM细胞中的表达高度受限,但大多数白血病无论其免疫表型如何均表达JL1。这些结果表明,JL1不仅是造血细胞的一种新型分化抗原,也是一种白血病相关抗原。因此,我们认为JL1是急性白血病诊断和免疫治疗中保护正常BM干细胞的候选分子。