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粒细胞集落刺激因子对移植人白血病的重症联合免疫缺陷小鼠造血细胞群的动员作用

G-CSF mobilization of haemopoietic cell populations in SCID mice engrafted with human leukaemia.

作者信息

Clutterbuck R D, Newman A, Powles R, Catovsky D, Millar J L

机构信息

Academic Department of Haematology and Cytogenetics, Institute of Cancer Research, Royal Marsden NHS Trust, Sutton, Surrey, UK.

出版信息

Bone Marrow Transplant. 1997 Aug;20(4):325-32. doi: 10.1038/sj.bmt.1700906.

DOI:10.1038/sj.bmt.1700906
PMID:9285548
Abstract

We have studied granulocyte colony-stimulating factor (G-CSF)-induced mobilization of haemopoietic cells in severe combined immune-deficient (SCID) mice engrafted with human leukaemia. Three leukaemia cell lines were investigated: the HL60 myeloblastic cell line, a chronic myeloid leukaemia (CML) xenograft cell line and an acute myeloid leukaemia (AML) xenograft line. Engraftment was detected using immunofluorescent staining of class I human leukocyte antigens and flow cytometry. All the tumours grew as disseminated disease with engraftment of bone marrow preceding involvement of peripheral blood (PB). After treatment with G-CSF (250 microg/kg/day) for 5 days, mobilization of haemopoietic progenitor cells (HPCs) was observed in non-engrafted SCID mice (40-fold) and in mice engrafted with human leukaemia (20-fold). G-CSF stimulated increases in PB HPCs and total numbers of host nucleated cells in leukaemia-bearing mice but did not induce rises in numbers of circulating HL60 colony-forming cells. Similarly, in mice engrafted with human CML or AML, G-CSF did not increase the number of malignant cells in the PB. These results provided evidence that the migration of normal and malignant haemopoietic cells into the PB are controlled by different mechanisms, and that contamination of PBSC harvests with leukaemic cells in SCID-human chimaeric mice is not enhanced by G-CSF-stimulated mobilization.

摘要

我们研究了粒细胞集落刺激因子(G-CSF)诱导的、移植了人类白血病的严重联合免疫缺陷(SCID)小鼠造血细胞的动员情况。研究了三种白血病细胞系:HL60髓母细胞系、一种慢性髓性白血病(CML)异种移植细胞系和一种急性髓性白血病(AML)异种移植系。使用I类人类白细胞抗原的免疫荧光染色和流式细胞术检测植入情况。所有肿瘤均以播散性疾病形式生长,骨髓植入先于外周血(PB)受累。用G-CSF(250μg/kg/天)治疗5天后,在未植入的SCID小鼠(40倍)和植入人类白血病的小鼠(20倍)中观察到造血祖细胞(HPCs)的动员。G-CSF刺激白血病荷瘤小鼠外周血HPCs和宿主有核细胞总数增加,但未诱导循环HL60集落形成细胞数量增加。同样,在植入人类CML或AML的小鼠中,G-CSF未增加外周血中恶性细胞的数量。这些结果证明,正常和恶性造血细胞向PB的迁移受不同机制控制,并且G-CSF刺激的动员不会增加SCID-人类嵌合小鼠中PBSC收获物被白血病细胞污染的情况。

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