The kinetics and extent of engraftment of chronic myelogenous leukemia cells in non-obese diabetic/severe combined immunodeficiency mice reflect the phase of the donor's disease: An in vivo model of chronic myelogenous leukemia biology
The kinetics and extent of engraftment of chronic myelogenous leukemia cells in non-obese diabetic/severe combined immunodeficiency mice reflect the phase of the donor's disease: An in vivo model of chronic myelogenous leukemia biology
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DOI：
10.1182/blood.v92.4.1390.416k09_1390_1396
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发表时间：
1998-08-15
期刊：
影响因子：
20.3
通讯作者：
Gordon, MY
中科院分区：
文献类型：
--
作者：
Dazzi, F;Capelli, D;Gordon, MY
对于慢性粒细胞白血病(CML)髓系扩张的动力学异常，体外研究几乎没有达成共识。因此，将人CML细胞移植到患有严重免疫缺陷疾病的非肥胖糖尿病小鼠(NOD/SCID小鼠)中可能是一个有用的模型。将慢性粒细胞白血病(CML)慢性期(CP)、加速期(AP)和急变期(BP)患者的外周血细胞和CML细胞系(BV173)注射到预照射的Noq/SCID小鼠体内。连续处死动物，取不同器官的细胞悬液和/或组织切片，用抗人CD45单抗(MoAbs)进行免疫组织化学和(或)流式细胞术检测，并用荧光原位杂交(FISH)检测bcr-abl融合基因。注射后一小时，细胞被隔离在肺和肝中，但两周后，这两个部位都不再检测到细胞。用铬-51标记的细胞也观察到了类似的短期动力学。4周时，BV173、AP和BE细胞在骨髓(BM)中首次出现植入迹象。8周时，小鼠骨髓中人类细胞比例的中位数分别为：CP 4%(范围1~9)，AP 11%(范围5~36)，BE 38.5%(范围18~79)，BV173 54%(范围31~69)。18~20周，CP细胞逐渐渗入骨髓(21%)和脾(6%)；注射该细胞系或BP细胞的动物均未存活超过12周。BP组的人体细胞数增长率(7.3%/周)高于CP组(0.9%/周)和AP组(0.5%/周)。用bcr和abl探针进行FISH分析表明，注射CP细胞后移植的相同人类细胞缺乏bcr-abl基因，推测是正常的。我们的结论是，慢性粒细胞白血病细胞在NOD/SCID小鼠体内的增殖动力学与供者疾病的阶段基本相同，从而提供了慢性粒细胞白血病生物学的体内模型。(C)1998年由美国血液病学会主办。
In vitro studies have provided little consensus on the kinetic abnormality underlying the myeloid expansion of chronic myelogenous leukemia (CML). Transplantation of human CML cells into non-obese diabetic mice with severe immunodeficiency disease (NOD/SCID mice) may therefore be a useful model. A CML cell line (BV173) and peripheral blood cells collected from CML patients in chronic phase (CP), accelerated phase (AP), or blastic phase (BP) were injected into preirradiated NOQ/SCID mice. Animals were killed at serial intervals; cell suspensions and/or tissue sections from different organs were studied by immunohistochemistry and/or flow cytometry using antihuman CD45 monoclonal antibodies (MoAbs), and by fluorescence in situ hybridization (FISH) for the BCR-ABL fusion gene. One hour after injection, cells were sequestered in the lungs and liver, but 2 weeks later they were no longer detectable in either site. Similar short-term kinetics were observed using Cr-51-labeled cells. The first signs of engraftment for BV173, AP, and BE cells were detected in the bone marrow (BM) at 4 weeks. At 8 weeks the median percentages of human cells in murine marrow were 4% (range, 1 to 9) for CP, 11% (range, 5 to 36) for AP, 38.5% (range, 18 to 79) for BE, and 54% (range, 31 to 69) for BV173. CP cells progressively infiltrated BM (21%) and spleen (6%) by 18 to 20 weeks; no animals injected with the cell line or BP cells survived beyond 12 weeks. The rate of increase in human cell numbers was higher for BP (7.3%/week) as compared with CP (0.9%/week) and AP (0.5%/week). FISH analysis with BCR and ABL probes showed that same of the human cells engrafting after injection of CP cells lacked a BCR-ABL gene and were presumably normal. We conclude that CML cells proliferate in NOD/SCID mice with kinetics that recapitulate the phase of the donor's disease, thus providing an in vivo model of CML biology. (C) 1998 by The American Society of Hematology.