Kamel-Reid S, Dick J E, Greaves A, Murdoch B, Doedens M, Grunberger T, Thorner P, Freedman M H, Phillips R A, Letarte M
Department of Genetics, Hospital for Sick Children, Toronto, Canada.
Leukemia. 1992 Jan;6(1):8-17.
The sensitivity of the scid mouse model was assessed by comparing the growth of two pre-B acute lymphoblastic leukemia (ALL) cell lines, A1 and G2, established from patients at relapse. When cell numbers varying from 10(4) to 10(7) were injected intravenously into scid mice, advanced growth and dissemination of leukemia was observed at 10-12 weeks with the G2 cells. Bone marrow, spleen and thymus contained high levels of human leukemic cells and infiltration into lung, kidney, liver, and brain was observed. Two of three mice grafted with only 100 cells showed high levels of infiltration at 15 weeks, suggesting that 100 G2 cells was near the limiting cell number that could produce disseminated leukemia. With the A1 line, a minimum of 10(5) cells was needed to obtain dissemination to liver, lung, brain, and kidney; a low level of spleen infiltration occurred and thymus invasion was not observed. In vitro, both lines showed a density dependent growth in clonogenic assays but the cloning efficiency of the A1 line was 10-fold higher than for G2 cells. These results indicate that G2 and A1 lines have a dissimilar aggressiveness in vivo which does not correlate with clonogenic assay in vitro. Neither G2 nor A1 lines, growing in vitro, expressed CD10/CALLA on their surface, despite low levels of antigen on the freshly obtained relapse samples. Although A1 cells remained CD10-negative in the scid mice, G2 cells showed detectable levels of CD10, particularly on those cells found in the thymus. Several subclones of the G2 line were derived from isolated colonies in vitro; they were found to be CD10- in vitro, but to become CD10+ when proliferating into scid mouse thymus, suggesting the induction of CD10 by the murine microenvironment.
通过比较从复发患者中建立的两种前B急性淋巴细胞白血病（ALL）细胞系A1和G2的生长情况，评估了严重联合免疫缺陷（scid）小鼠模型的敏感性。当将数量从10⁴到10⁷不等的细胞静脉注射到scid小鼠体内时，在10至12周时观察到G2细胞导致白血病的进展性生长和扩散。骨髓、脾脏和胸腺中含有高水平的人白血病细胞，并观察到其浸润到肺、肾、肝和脑。三只仅移植了100个细胞的小鼠中有两只在15周时显示出高水平的浸润，这表明100个G2细胞接近能够产生播散性白血病的极限细胞数。对于A1细胞系，至少需要10⁵个细胞才能扩散到肝脏、肺、脑和肾脏；脾脏有低水平的浸润，但未观察到胸腺浸润。在体外，两种细胞系在克隆形成试验中均显示出密度依赖性生长，但A1细胞系的克隆效率比G2细胞高10倍。这些结果表明，G2和A1细胞系在体内具有不同的侵袭性，这与体外克隆形成试验无关。在体外生长的G2和A1细胞系表面均不表达CD10/普通急性淋巴细胞白血病抗原（CALLA），尽管在新鲜获得的复发样本中抗原水平较低。尽管A1细胞在scid小鼠中仍为CD10阴性，但G2细胞显示出可检测水平的CD10，特别是在胸腺中发现的那些细胞上。G2细胞系中的几个亚克隆源自体外分离的集落；它们在体外被发现为CD10阴性，但在增殖进入scid小鼠胸腺时变为CD10阳性，这表明小鼠微环境诱导了CD10的表达。
