Department of Hematology/Oncology, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8606, Japan.
J Oncol. 2012;2012:901783. doi: 10.1155/2012/901783. Epub 2012 Jul 15.
We recently reported that chronic myelogenous leukemia (CML) cells converted into myofibroblasts to create a microenvironment for proliferation of CML cells in vitro. To analyze a biological contribution of CML-derived myofibroblasts in vivo, we observed the characters of leukemic nonobese diabetes/severe combined immunodeficiency (NOD/SCID) mouse. Bone marrow nonadherent mononuclear cells as well as human CD45-positive cells obtained from CML patients were injected to the irradiated NOD/SCID mice. When the chimeric BCR-ABL transcript was demonstrated in blood, human CML cells were detected in NOD/SCID murine bone marrow. And CML-derived myofibroblasts composed with the bone marrow-stroma, which produced significant amounts of human vascular endothelial growth factor A. When the parental CML cells were cultured with myofibroblasts separated from CML cell-engrafted NOD/SCID murine bone marrow, CML cells proliferated significantly. These observations indicate that CML cells make an adequate microenvironment for their own proliferation in vivo.
我们最近报道称,慢性髓性白血病(CML)细胞转化为肌成纤维细胞,在体外为 CML 细胞的增殖创造了微环境。为了分析 CML 衍生的肌成纤维细胞在体内的生物学贡献,我们观察了白血病非肥胖型糖尿病/重症联合免疫缺陷(NOD/SCID)小鼠的特征。将骨髓非贴壁单核细胞以及从 CML 患者获得的人 CD45 阳性细胞注射到辐照的 NOD/SCID 小鼠中。当在血液中证明存在嵌合 BCR-ABL 转录本时,在 NOD/SCID 鼠骨髓中检测到人类 CML 细胞。并且 CML 衍生的肌成纤维细胞与骨髓基质组成,产生大量的人血管内皮生长因子 A。当将亲本 CML 细胞与从 CML 细胞移植的 NOD/SCID 鼠骨髓中分离的肌成纤维细胞共培养时,CML 细胞显著增殖。这些观察结果表明,CML 细胞在体内为自身增殖创造了适宜的微环境。