Sawada K, Koizumi K, Tarumi T, Takano H, Ieko M, Nishio M, Fukada Y, Yasukouchi T, Yamaguchi M, Koike T
Department of Medicine II, Hokkaido University School of Medicine, Sapporo, Japan.
Leuk Res. 1999 Jan;23(1):1-11. doi: 10.1016/s0145-2126(98)00128-3.
The stem cell factor (SCF: a ligand for c-kit) plays a central role in the growth of myelodysplastic (MDS) progenitor cells with leukemic type growth. In this study, the role of physiologic concentrations of SCF on the proliferation and differentiation on MDS progenitor cells was further analyzed in the presence of combined cytokines. For this purpose, marrow CD34+ cells were purified up to 94% for 12 normal individuals and 90% for 18 MDS patients, using monoclonal antibodies and immunomagnetic microspheres. The purified CD34+ cells were cultured for 14 days with saturating doses of cytokines, including recombinant human macrophage colony stimulating factor (rM-CSF), granulocyte-CSF (rG-CSF), granulocyte/macrophage-CSF (rGM-CSF), interleukin-3 (rIL-3) and rSCF. The clonal growth of MDS CD34+ cells supported by a combination of all the above cytokines was then subdivided into the two patterns of leukemic or non-leukemic. The role of various concentrations of rSCF (0, 0.5, 5, 50 and 500 ng ml(-1)), with or without the above cytokines, in proliferation and differentiation of MDS CD34+ cells was analyzed in each group. The physiologic concentration of SCF at 5 ng ml(-1) significantly increased undifferentiated 'blast cell' colonies or clusters in leukemic type growth of MDS CD34+ cells over that seen in normal CD34+ cells. SCF is present in plasma at a level of ng ml(-1). This means that progenitor cells are continuously exposed to stimulation by SCF in vivo and that MDS leukemic cells have a growth advantage over normal blasts.
干细胞因子（SCF：c-kit的配体）在具有白血病样生长的骨髓增生异常综合征（MDS）祖细胞的生长中起核心作用。在本研究中，在联合细胞因子存在的情况下，进一步分析了生理浓度的SCF对MDS祖细胞增殖和分化的作用。为此，使用单克隆抗体和免疫磁珠，对12名正常个体的骨髓CD34+细胞进行纯化，纯度高达94%，对18名MDS患者的骨髓CD34+细胞进行纯化，纯度达90%。将纯化的CD34+细胞与饱和剂量的细胞因子一起培养14天，这些细胞因子包括重组人巨噬细胞集落刺激因子（rM-CSF）、粒细胞集落刺激因子（rG-CSF）、粒细胞/巨噬细胞集落刺激因子（rGM-CSF）、白细胞介素-3（rIL-3）和rSCF。然后，将上述所有细胞因子联合支持的MDS CD34+细胞的克隆生长细分为白血病或非白血病两种模式。分析了每组中不同浓度的rSCF（0、0.5、5、50和500 ng ml-1）在有或无上述细胞因子情况下对MDS CD34+细胞增殖和分化的作用。5 ng ml-1的SCF生理浓度使MDS CD34+细胞白血病样生长中未分化的“原始细胞”集落或簇显著增加，高于正常CD34+细胞中的情况。SCF在血浆中的水平为ng ml-1。这意味着祖细胞在体内持续受到SCF的刺激，且MDS白血病细胞比正常原始细胞具有生长优势。
