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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Induction in myeloid leukemic cells of genes that are expressed in different normal tissues.
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Induction in myeloid leukemic cells of genes that are expressed in different normal tissues.

机译:在髓样白血病细胞中诱导在不同正常组织中表达的基因。

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Using DNA microarray and cluster analysis of expressed genes in a cloned line (M1-t-p53) of myeloid leukemic cells, we have analyzed the expression of genes that are preferentially expressed in different normal tissues. Clustering of 547 highly expressed genes in these leukemic cells showed 38 genes preferentially expressed in normal hematopoietic tissues and 122 other genes preferentially expressed in different normal nonhematopoietic tissues, including neuronal tissues, muscle, liver, and testis. We have also analyzed the genes whose expression in the leukemic cells changed after activation of WT p53 and treatment with the cytokine IL-6 or the calcium mobilizer thapsigargin. Of 620 such genes in the leukemic cells that were differentially expressed in normal tissues, clustering showed 80 genes that were preferentially expressed in hematopoietic tissues and 132 genes in different normal nonhematopoietic tissues that also included neuronal tissues, muscle, liver, and testis. Activation of p53 and treatment with IL-6 or thapsigargin induced different changes in the genes preferentially expressed in these normal tissues. These myeloid leukemic cells thus express genes that are expressed in normal nonhematopoietic tissues, and various treatments can reprogram these cells to induce other such nonhematopoietic genes. The results indicate that these leukemic cells share with normal hematopoietic stem cells the plasticity of differentiation to different cell types. It is suggested that this reprogramming to induce in malignant cells genes that are expressed in different normal tissues may be of clinical value in therapy.
机译:使用DNA芯片和髓系白血病细胞克隆系(M1-t-p53)中表达基因的聚类分析,我们分析了优先在不同正常组织中表达的基因的表达。这些白血病细胞中547个高表达基因的聚类显示,在正常造血组织中优先表达的基因有38个,在不同的正常非造血组织(包括神经元组织,肌肉,肝脏和睾丸)中优先表达的其他122个基因。我们还分析了WT p53激活并用细胞因子IL-6或钙动员毒胡萝卜素处理后白血病细胞中表达改变的基因。在正常组织中差异表达的白血病细胞中的620个此类基因中,聚类显示80个基因优先在造血组织中表达,132个基因在不同的正常非造血组织中也包括神经元组织,肌肉,肝脏和睾丸。 p53的激活和IL-6或毒胡萝卜素的处理会诱导这些正常组织中优先表达的基因发生不同的变化。因此,这些骨髓性白血病细胞表达在正常非造血组织中表达的基因,并且各种治疗可以重新编程这些细胞以诱导其他此类非造血基因。结果表明,这些白血病细胞与正常的造血干细胞具有向不同细胞类型分化的可塑性。提示这种重新编程以在恶性细胞中诱导在不同正常组织中表达的基因可能在治疗中具有临床价值。

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