High level engraftment of NOD/SCID mice by primitive normal and leukemic hematopoietic cells from patients with chronic myeloid leukemia in chronic phase
High level engraftment of NOD/SCID mice by primitive normal and leukemic hematopoietic cells from patients with chronic myeloid leukemia in chronic phase
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DOI：
10.1182/blood.v91.7.2406.2406_2406_2414
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发表时间：
1998-04-01
期刊：
影响因子：
20.3
通讯作者：
Dick, JE
中科院分区：
文献类型：
--
作者：
Wang, JCY;Lapidot, T;Dick, JE
我们之前已经证明，静脉注射来自新诊断的慢性髓性白血病（CML）患者的外周血（PB）或骨髓（BM）细胞可以移植亚致死照射的严重联合免疫缺陷（SCID）小鼠的骨髓。我们现在报告了非肥胖糖尿病(NOD)/SCID受者的慢性期CML细胞移植结果，显示了后者模型的优越性。点头/ SCID小鼠的移植与7 - 10 x 10(7)病人铅或BM细胞导致的持续存在人体细胞在大英博物馆的老鼠长达7个月,和原始人类CD34(+)细胞克隆形成细胞(CFC)包括那些被发现,作为长期culture-initiating细胞,或由coexpression Thy-1,被发现在一个更高比例的点头/ SCID接受者分析,和比以前在SCID接受者。移植CML细胞的NOD/SCID小鼠骨髓中存在的人类CFC和总人类细胞也比SCID模型中获得的白血病细胞比例更高，并且可以用CML患者富集的CD34（+）细胞移植NOD/SCID小鼠。这些结果表明，NOD/SCID小鼠可能允许更多的正常和白血病（Ph+）细胞的植入和扩增，足以定量和表征CML患者中存在的正常和白血病干细胞。此外，该模型应该使研究疾病进展的机制和开发更有效的体内治疗成为可能。(C) 1998年由美国血液病学会出版。
We have previously shown that intravenously injected peripheral blood (PB) or bone marrow (BM) cells from newly diagnosed chronic myeloid leukemia (CML) patients can engraft the BM of sublethally irradiated severe combined immunodeficient (SCID) mice. We now report engraftment results for chronic phase CML cells in nonobese diabetic (NOD)/SCID recipients which show the superiority of this latter model. Transplantation of NOD/SCID mice with 7 to 10 x 10(7) patient PB or BM cells resulted in the continuing presence of human cells in the BM of the mice for up to 7 months, and primitive human CD34(+) cells, including those detectable as colony-forming cells (CFC), as long-term culture-initiating cells, or by their coexpression of Thy-1, were found in a higher proportion of the NOD/SCID recipients analyzed, and at higher levels than were seen previously in SCID recipients. The human CFC and total human cells present in the BM of the NOD/SCID mice transplanted with CML cells also contained higher proportions of leukemic cells than were obtained in the SCID model, and NOD/SCID mice could be repopulated with transplants of enriched CD34(+) cells from patients with CML. These results suggest that the NOD/SCID mouse may allow greater engraftment and amplification of both normal and leukemic (Ph+) cells sufficient for the quantitation and characterization of the normal and leukemic stem cells present in patients with CML. In addition, this model should make practical the investigation of mechanisms underlying progression of the disease and the development of more effective in vivo therapies. (C) 1998 by The American Society of Hematology.