Homing, proliferation and survival sites of human leukemia cells in vivo in immunodeficient mice
Homing, proliferation and survival sites of human leukemia cells in vivo in immunodeficient mice
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DOI：
10.1038/sj.leu.2404432
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发表时间：
2007-01-01
期刊：
影响因子：
11.4
通讯作者：
Naoe, T.
中科院分区：
文献类型：
--
作者：
Ninomiya, M.;Abe, A.;Naoe, T.
造血干细胞龛的细胞成分已逐渐确定。然而，恶性造血的生态位仍有待阐明。本研究利用人白血病细胞移植到免疫缺陷小鼠体内，通过免疫组织病理学方法研究了白血病细胞在小鼠体内的归巢、增殖和存活部位，并与脐血CD 34（+）（CBCD 34（+））细胞的相应部位进行了比较。人白血病细胞最初定位于骨骺区成骨细胞表面，4周内扩展至血管内和骨干区。骨髓中CD 34（+）白血病细胞的百分比一过性升高至50%。体内5-溴-2 '-脱氧尿苷标记显示，骨骺是白血病细胞增殖最活跃的部位。CBCD 34（+）细胞具有与白血病细胞相似的归巢和增殖模式。在给予高剂量胞嘧啶-1-β-D-阿拉伯呋喃糖苷后，残留的白血病细胞位于血管周围内皮以及与骨小梁内膜接触。这些发现表明，异种移植到免疫缺陷小鼠中为研究白血病生态位提供了一个有用的模型。
The cellular components of the hematopoietic stem cell niche have been gradually identified. However, the niche for malignant hematopoiesis remains to be elucidated. Here, using human leukemia cells, which could be transplanted to immunodeficient mice, we studied the in vivo homing, proliferation and survival sites by immunohistopathology, compared with the corresponding sites for cord blood CD34(+) ( CBCD34(+)) cells. The human leukemia cells initially localized on the surface of osteoblasts in the epiphysial region, and expanded to the inner vascular and diaphysial regions within 4 weeks. The percentage of CD34(+) leukemia cells in the bone marrow was transiently increased up to 50%. In vivo 5-bromo-2'-deoxyuridine labeling revealed that the epiphysis was the most active site for leukemia cell proliferation. CBCD34(+) cells showed the similar pattern of homing and proliferation to leukemia cells. After high-dose administration of cytosine-1-beta-D-arabinofuranoside, residual leukemia cells were localized in the perivascular endothelium as well as in contact with the trabecular endosteum. These findings suggest that xenotransplantation into immunodeficient mice provides a useful model to study the leukemia niche.