Filshie R J, Zannettino A C, Makrynikola V, Gronthos S, Henniker A J, Bendall L J, Gottlieb D J, Simmons P J, Bradstock K F
Department of Haematology, Westmead Hospital, New South Wales, Australia.
Leukemia. 1998 Mar;12(3):414-21. doi: 10.1038/sj.leu.2400922.
Despite the importance of bone marrow stromal cells in hemopoiesis, the profile of surface molecule expression is relatively poorly understood. Mice were immunized with cultured human bone marrow stromal cells in order to raise monoclonal antibodies to novel cell surface molecules, which might be involved in interactions with hemopoietic cells. Three antibodies, WM85, CC9 and EB4 were produced, and were found to identify a 100-110 kDa antigen on bone marrow fibroblasts. Molecular cloning revealed the molecule to be MUC18 (CD146), a member of the immunoglobulin superfamily, previously described as a marker of metastatic melanoma. In addition to the expected expression on melanoma cell lines and endothelial cells, a number of human leukemic cell lines were found to express MUC18, including all six T leukemia lines tested, one of five B lineage lines and one of four myeloid lines. Analysis of bone marrow samples from patients revealed positivity in 20% of B lineage ALL (n = 20), one of three T-ALL, 15% of AML (n = 13) and 43% of various B lymphoproliferative disorders (n = 7). No apparent reactivity was observed with mononuclear cells from normal peripheral blood or bone marrow, including candidate hemopoietic stem cells characterized by their expression of the CD34 antigen. However, positive selection of bone marrow mononuclear cells labeled with MUC18 antibody revealed a rare subpopulation (<1%) containing more than 90% of the stromal precursors identified in fibroblast colony-forming assays. The structure and tissue distribution of MUC18 suggest a functional role in regulation of hemopoiesis.
尽管骨髓基质细胞在造血过程中很重要，但其表面分子表达谱却相对了解较少。用培养的人骨髓基质细胞免疫小鼠，以产生针对可能参与与造血细胞相互作用的新型细胞表面分子的单克隆抗体。产生了三种抗体，即WM85、CC9和EB4，发现它们能识别骨髓成纤维细胞上一种100 - 110 kDa的抗原。分子克隆显示该分子为MUC18（CD146），属于免疫球蛋白超家族成员，此前被描述为转移性黑色素瘤的标志物。除了在黑色素瘤细胞系和内皮细胞上的预期表达外，还发现一些人白血病细胞系表达MUC18，包括所检测的全部六种T白血病细胞系、五种B系细胞系中的一种以及四种髓系细胞系中的一种。对患者骨髓样本的分析显示，20%的B系急性淋巴细胞白血病（n = 20）、三例T - 急性淋巴细胞白血病中的一例、15%的急性髓系白血病（n = 13）以及43%的各种B淋巴细胞增殖性疾病（n = 7）呈阳性反应。未观察到与正常外周血或骨髓的单核细胞有明显反应，包括以表达CD34抗原为特征的候选造血干细胞。然而，用MUC18抗体标记的骨髓单核细胞的阳性选择揭示了一个罕见的亚群（<1%），其中包含在成纤维细胞集落形成试验中鉴定出的超过90%的基质前体。MUC18的结构和组织分布表明其在造血调节中具有功能作用。
