Good engraftment of B-cell precursor ALL in NOD-SCID mice
Good engraftment of B-cell precursor ALL in NOD-SCID mice
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DOI：
10.1055/s-2008-1043947
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发表时间：
1997-07-01
影响因子：
1
通讯作者：
Vormoor, J
中科院分区：
文献类型：
--
作者：
Baersch, G;Mollers, T;Vormoor, J
背景通过将人白血病细胞移植到免疫缺陷的SCID小鼠体内，建立了人B细胞前体ALL的体内模型。高危和复发的白血病在这些小鼠身上移植得很好，然而，预后良好的儿童ALL往往生长得很差。最近，通过将SCID突变与NOD小鼠背景杂交，培育出了一种新的、更具免疫缺陷的小鼠品系。由于这些NOD-SCID泥被证明是更好的人类髓系细胞的接受者，本研究的目的是测试这些小鼠作为人类急性淋巴细胞白血病细胞的宿主。患者和方法7名儿童和1名成人B细胞前体患者的骨髓或外周血细胞均按既定方案移植到免疫缺陷NOD-SCID小鼠。主要结果8例患者中有6例(75%)全部细胞移植到NOD-SCID小鼠，4例患者(50%)导致白血病在小鼠骨髓中广泛渗透(>；10%)。可以证明高水平的人体细胞植入。通过流式细胞术、Southern印迹分析和细胞学检测。从细胞学和免疫表型来看，小鼠的白血病与患者的原始白血病没有区别，高度移植的小鼠骨髓中几乎没有人嗜酸性粒细胞的存在，这表明残留的正常细胞只有很少的共植入。不同患者的细胞移植后，小鼠显性白血病的发生时间从1.5个月到7个月不等。有趣的是，与髓系细胞不同的是，通过亚致死剂量辐射对小鼠进行预适应并不是成功植入的必要条件。1例患者白血病细胞的极限稀释实验表明，仅10000个细胞就足以将白血病转移到NOD-SCID小鼠身上。结论NOD-SCID小鼠是人ALL的敏感受体。
Background In vivo models for human B cell precursor ALL have been established by transplanting human leukemic cells onto immune-deficient SCID mice. High risk and relapsed leukemias engraft very well in these mice, however, good prognosis pediatric ALL often grow poorly if at all. Recently a new, even more immune-deficient mouse strain has been bred by crossing the scid mutation onto the NOD mouse background. As these NOD-SCID mire have been shown to be better recipients for human myeloid cells the goal of this study was to test these mice as hosts for human acute lymphoblastic leukemia cells.Patients and methods Bone marrow or peripheral blood cells from 7 pediatric and one adult patient with B-cell precursor ALL were transplanted onto immune-deficient NOD-SCID mice according to established protocols.Main results ALL cells from 6 out of the 8 patients (75%) successfully engrafted the NOD-SCID mice and from 4 patients (50%) led to an extensive leukemic infiltration in the murine marrow (>10%). High level human cell engraftment could be demonstrated. by flow cytometry, Southern blot analysis and cytology. By cytology and immunophenotype the leukemia in the mice was indistinguishable from the original leukemia in the patients, The presence of few human eosinophils in the marrow of highly engrafted mice indicates minimal coengraftment of residual normal cells. Development of overt leukemia in the mice after transplantation of cells from different patients varied between 1.5 and 7 months. Interestingly and in contrast to myeloid cells, conditioning of the mice by sublethal irradiation was not necessary for successful engraftment. Limiting dilution experiments with leukemic blasts from one patient showed that as few as 10 000 cells were sufficient to transfer the leukemia onto NOD-SCID mice.Conclusions NOD-SCID mice are sensitive recipients for human ALL xenografts.