ESAM is a novel human hematopoietic stem cell marker associated with a subset of human leukemias

ESAM is a novel human hematopoietic stem cell marker associated with a subset of human leukemias
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DOI:
10.1016/j.exphem.2015.12.010
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发表时间:
2016-04-01
影响因子:
2.6
通讯作者:
Kanakura, Yuzuru
Kanakura, Yuzuru
中科院分区:
医学4区
文献类型:
--
作者:
Ishibashi, Tomohiko;Yokota, Takafumi;Kanakura, Yuzuru

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可靠的标记物对于提高我们对人类造血干细胞生物学特性的理解以及促进造血干细胞在移植和再生医学领域的应用至关重要。我们以前确定内皮细胞选择性粘附分子(ESAM)作为一种新的造血干细胞在小鼠的功能标志物。在这里,我们发现ESAM也可以用于从所有目前可用的来源(成人骨髓、动员的外周血和脐带血)纯化人造血干细胞。免疫缺陷小鼠中的多能集落形成单位和长期造血重建细胞仅存在于CD 34(+)CD 38(-)细胞的ESAM(高)部分。脐带血和胶原酶处理的骨髓的CD 34(+)CD 38(-)部分含有表现出极高ESAM表达的细胞;这些细胞可能与内皮细胞系相关。红系和巨核细胞来源的白血病细胞系,但不是髓系或淋巴系,ESAM阳性。然而,在一些原发性急性髓系白血病细胞中观察到高ESAM表达。此外,KG-1a髓性白血病细胞在体内通过反复的白血病重建从ESAM阴性转变为ESAM阳性。因此,ESAM是研究人类造血干细胞和白血病细胞的有用标记物。版权所有(C)2016 ISEH -国际实验血液学学会。爱思唯尔公司出版
Reliable markers are essential to increase our understanding of the biological features of human hematopoietic stem cells and to facilitate the application of hematopoietic stem cells in the field of transplantation and regenerative medicine. We previously identified endothelial cell-selective adhesion molecule (ESAM) as a novel functional marker of hematopoietic stem cells in mice. Here, we found that ESAM can also be used to purify human hematopoietic stem cells from all the currently available sources (adult bone marrow, mobilized peripheral blood, and cord blood). Multipotent colony-forming units and long-term hematopoietic-reconstituting cells in immunodeficient mice were found exclusively in the ESAM(High) fraction of CD34(+)CD38(-) cells. The CD34(+)CD38(-) fraction of cord blood and collagenase-treated bone marrow contained cells exhibiting extremely high expression of ESAM; these cells are likely to be related to the endothelial lineage. Leukemia cell lines of erythroid and megakaryocyte origin, but not those of myeloid or lymphoid descent, were ESAM positive. However, high ESAM expression was observed in some primary acute myeloid leukemia cells. Furthermore, KG-1a myeloid leukemia cells switched from ESAM negative to ESAM positive with repeated leukemia reconstitution in vivo. Thus, ESAM is a useful marker for studying both human hematopoietic stem cells and leukemia cells. Copyright (C) 2016 ISEH - International Society for Experimental Hematology. Published by Elsevier Inc.