Differentiation-inducing effect of recombinant human tumor necrosis factor alpha and gamma-interferon in vitro on blast cells from patients with acute myeloid leukemia and myeloid blast crisis of chronic myeloid leukemia.
Differentiation-inducing effect of recombinant human tumor necrosis factor alpha and gamma-interferon in vitro on blast cells from patients with acute myeloid leukemia and myeloid blast crisis of chronic myeloid leukemia.
复制标题
DOI：
--
复制
发表时间：
1989-06
期刊：
影响因子：
11.2
通讯作者：
K. Geissler;G. Tricot;T. Leemhuis;E. Walker;H. Broxmeyer
中科院分区：
文献类型：
--
作者：
K. Geissler;G. Tricot;T. Leemhuis;E. Walker;H. Broxmeyer
肿瘤坏死因子α（TNF-α）和γ-干扰素（IFN-γ）已被证明可以抑制含有急性髓性白血病患者原始细胞的培养物中的克隆形成生长。我们报告说，重组人TNF-α和IFN-γ也能够诱导功能和形态成熟的新鲜髓系白血病细胞在体外。评估含有来自急性髓性白血病（11名患者）或慢性髓性白血病的髓性原始细胞危象（5名患者）的细胞的悬浮培养物，发现与不含细胞因子的对照培养物相比，重组人TNF-α和IFN-γ显著增加了还原硝基蓝四唑的细胞的数量（分别为P小于0.001和P小于0.001）。反应者的细胞显示单核细胞/巨噬细胞分化，粘附到塑料表面，α-醋酸萘酯酶阳性染色的发展，典型的形态学和单克隆抗体Mo-1，Mo-2和My-4检测到的细胞表面抗原的表达特征的改变。这两种细胞因子减少了悬浮培养中的活细胞数、原始细胞数和簇形成单位数，表明对白血病细胞的生长能力具有抑制作用。与单独的任一因子的最大效应相比，重组人TNF-α和IFN-γ的组合显著增加了生长抑制和细胞粘附的程度，但没有导致硝基蓝四唑还原的进一步增加。在IFN-γ或TNF-α分化诱导的巨噬细胞中存在奥尔杆和来自M5急性髓性白血病患者的细胞，表明这些细胞因子可以诱导来自白血病患者的原代细胞中白血病克隆的分化。
Tumor necrosis factor alpha (TNF-alpha) and gamma-interferon (IFN-gamma) have been shown to suppress clonogenic growth in cultures containing blast cells obtained from patients with acute myeloid leukemia. We report that recombinant human TNF-alpha and IFN-gamma are also able to induce functional and morphological maturation in fresh myeloid leukemic cells in vitro. Assessing suspension cultures containing cells from patients with acute myeloid leukemia (11 patients) or myeloid blast crisis of chronic myeloid leukemia (5 patients), it was found that recombinant human TNF-alpha and IFN-gamma significantly enhanced the number of cells reducing nitroblue tetrazolium, as compared to control cultures containing no cytokine (P less than 0.001 and P less than 0.001, respectively). Cells from responders showed alterations characteristic of monocyte/macrophage differentiation, adherence to plastic surfaces, development of positive staining for alpha-naphthyl acetate esterase, typical morphology, and expression of cell surface antigens detected by the monoclonal antibodies Mo-1, Mo-2, and My-4. Both cytokines decreased the number of viable cells, the number of blast cells, and the number of cluster-forming units in suspension culture, suggesting inhibitory actions on the growth capacity of leukemic cells. Compared to the maximum effects of either factor alone, the combination of recombinant human TNF-alpha and IFN-gamma significantly increased the extent of growth inhibition and cell adherence but did not result in further increases in nitroblue tetrazolium reduction. The presence of Auer rods in IFN-gamma or TNF-alpha differentiation-induced macrophages with cells from a patient with M5 acute myeloid leukemia demonstrates that these cytokines can induce differentiation of a leukemic clone in primary cells from patients with leukemia.