Ishii E, Greaves A, Grunberger T, Freedman M H, Letarte M
Division of Immunology/Cancer Research, Hospital for Sick Children, Toronto, Canada.
Leukemia. 1993 Oct;7(10):1592-601.
We have previously demonstrated the engraftment and dissemination of human pre-B acute lymphoblastic leukemia (ALL) cells into scid mice. In the current study, the temporal pattern of infiltration of a CD10- pre-B leukemia line (G2) in various murine tissues and the progression of the disease in the whole animal were monitored by quantifying human CD44 mRNA expression by the polymerase chain reaction (PCR). Irradiated scid mice were injected intravenously with 10(6) G2 cells and killed 3 days to 10 weeks later. After 2 weeks, leukemic cells were found mostly in bone marrow, but also in lung. At 6 to 7 weeks, spleen and lung contained 30% human RNA, while peripheral blood, liver, and kidney contained 2-3%. Infiltration to brain and thymus was observed at 8-9 weeks. In terms of the whole animal, spleen and liver were the major sites of tumor burden. The induction of CD10 expression was previously observed in transplanted CD10- G2 leukemic cells recovered from scid thymus at 10-12 weeks, which corresponds to the terminal stage of disease. In this study, the CD10 expression on the leukemic cells was monitored at earlier time points by flow cytometry and quantitative PCR. Induction of CD10 was first observed in bone marrow, spleen, peripheral blood, and liver at 6-7 weeks (10-fold), at the time of the onset of dissemination of the leukemia. Despite the presence of 30% human RNA in lung at 6-7 weeks, CD10 induction was not significant in that site before 10 weeks. Increased levels of CD10 were seen in all tissues between 8 and 10 weeks; the highest levels were observed in leukemic cells proliferating in thymus (113-fold) and in those found in circulation. These findings suggest that initial induction of CD10 occurs in hematopoietic tissues at the time of rapid proliferation of the leukemic cells and their infiltration of several tissues. At later time points, the increase in CD10 expression is seen on the leukemic cells found in all peripheral organs suggesting an association with disease progression.
我们之前已证明人前B急性淋巴细胞白血病（ALL）细胞能植入并扩散至重度联合免疫缺陷（scid）小鼠体内。在当前研究中，通过聚合酶链反应（PCR）定量检测人CD44 mRNA表达，监测了CD10阴性前B白血病细胞系（G2）在各种小鼠组织中的浸润时间模式以及整个动物体内疾病的进展情况。给经照射的scid小鼠静脉注射10⁶个G2细胞，3天后至10周后将其处死。2周后，白血病细胞主要见于骨髓，但也见于肺。6至7周时，脾脏和肺中含30%的人RNA，而外周血、肝脏和肾脏中含2 - 3%。8至9周时观察到白血病细胞浸润至脑和胸腺。就整个动物而言，脾脏和肝脏是肿瘤负荷的主要部位。之前在10至12周从scid胸腺中回收的移植CD10阴性G2白血病细胞中观察到CD10表达的诱导，这与疾病的终末期相对应。在本研究中，通过流式细胞术和定量PCR在更早的时间点监测白血病细胞上的CD10表达。在6至7周（白血病开始扩散时），首次在骨髓、脾脏、外周血和肝脏中观察到CD10的诱导（增加10倍）。尽管在6至7周时肺中存在30%的人RNA，但在10周前该部位CD10的诱导并不显著。在8至10周期间，所有组织中的CD10水平均升高；在胸腺中增殖的白血病细胞（增加113倍）以及循环中的白血病细胞中观察到最高水平。这些发现表明，CD10的初始诱导发生在白血病细胞快速增殖并浸润至多个组织时的造血组织中。在随后的时间点，在所有外周器官中的白血病细胞上均可见CD10表达增加，提示其与疾病进展相关。
