Hayashi M, Okabe-Kado J, Hozumi M
Department of Chemotherapy, Saitama Cancer Center Research Institute, Japan.
Leuk Res. 1989;13(11):989-99. doi: 10.1016/0145-2126(89)90006-4.
We developed an experimental model to investigate in vivo differentiation and proliferation of leukemia cells using mouse myeloid leukemia aneuploid cells (LL-2) and syngeneic SL mice. The LL-2 cells were near-tetraploid cells isolated from mouse myeloid leukemia cell line M1 (clone D501). In suspension culture, the LL-2 cells were myeloblastic and grew well like parent D501 cells, but were distinct from the parental cells due to the large size of their nucleus, double chromosome number and DNA content. The LL-2 cells as well as D501 cells could be induced to differentiate in vitro into mature macrophage-like cells by a protein inducer of differentiation. After transplantation of 4 X 10(6) LL-2 cells into the intraperitoneal cavity of syngeneic SL mice, most of them died of leukemia within 10 weeks. On microscopic examination of the peritoneal cells of the mice, the transplanted LL-2 cells were clearly distinguishable from normal host cells by the size of their nucleus. We determined the increase in the LL-2 cells in the peritoneal cavity by morphological examination of the large-sized LL-2 cells. Survival times of the mice inoculated with the LL-2 cells were prolonged by administrations of an inducer of differentiation, poly(I).poly(C). We found morphological changes in the peritoneal blastic LL-2 cells to mature macrophage-like cells after the serial administrations of poly(I).poly(C) to the recipient mice. Thus the aneuploid LL-2 cells that grow in syngeneic mice may be useful to study in vivo differentiation and proliferation of leukemia cells, and to develop a therapeutic strategy of leukemia using various treatments including differentiation inducers.
我们利用小鼠髓系白血病非整倍体细胞（LL-2）和同基因SL小鼠建立了一个实验模型，以研究白血病细胞在体内的分化和增殖。LL-2细胞是从小鼠髓系白血病细胞系M1（克隆D501）分离得到的近四倍体细胞。在悬浮培养中，LL-2细胞呈髓母细胞样，像亲本D501细胞一样生长良好，但由于其细胞核大、染色体数目和DNA含量加倍，与亲本细胞不同。LL-2细胞以及D501细胞可通过一种分化蛋白诱导剂在体外诱导分化为成熟的巨噬细胞样细胞。将4×10⁶个LL-2细胞移植到同基因SL小鼠的腹腔后，大多数小鼠在10周内死于白血病。在对小鼠腹腔细胞进行显微镜检查时，移植的LL-2细胞可通过其细胞核大小与正常宿主细胞明显区分开来。我们通过对大型LL-2细胞进行形态学检查来确定腹腔中LL-2细胞的增加情况。通过给予分化诱导剂聚肌苷酸-聚胞苷酸（poly(I).poly(C)），接种LL-2细胞的小鼠存活时间得以延长。在对受体小鼠连续给予poly(I).poly(C)后，我们发现腹腔中母细胞样的LL-2细胞出现了向成熟巨噬细胞样细胞的形态学变化。因此，在同基因小鼠中生长的非整倍体LL-2细胞可能有助于研究白血病细胞在体内的分化和增殖，并有助于开发包括分化诱导剂在内的各种治疗方法的白血病治疗策略。
