Megakaryocytic differentiation in human chronic myelogenous leukemia K562 cells induced by ionizing radiation in combination with phorbol 12-myristate 13-acetate.
Megakaryocytic differentiation in human chronic myelogenous leukemia K562 cells induced by ionizing radiation in combination with phorbol 12-myristate 13-acetate.
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DOI：
10.1093/jrr/rrs125
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发表时间：
2013-05
影响因子：
2
通讯作者：
Kashiwakura I
中科院分区：
文献类型：
--
作者：
Hirose K;Monzen S;Sato H;Sato M;Aoki M;Hatayama Y;Kawaguchi H;Narita Y;Takai Y;Kashiwakura I
分化诱导治疗是白血病治疗的一种有吸引力的方法。研究表明，细胞内活性氧（ROS）的积累参与了phorbol 12-肉豆蔻酸13-乙酸酯（PMA）诱导K562白血病细胞系巨核细胞分化的过程。因此，ros诱导技术可能是诱导分化的一种有效方法。因此，我们假设电离辐射通过白血病细胞内ROS的积累加速了巨核细胞的分化。在本研究中，电离辐射被证明可以促进pma诱导的巨核细胞分化。CD41高表达的细胞能有效维持细胞内ROS水平。发现电离辐射对分化的增强是通过丝裂原活化蛋白激酶（MAPK）途径调节的，包括细胞外信号调节蛋白激酶1/2 （ERK1/2）和p38 MAPK。电离辐射还控制氧化应激反应基因血红素加氧酶-1 （HO1）的mRNA表达。因此，我们得出结论，电离辐射增加的细胞内ROS调节了MAPK途径下游的巨核细胞分化。
Differentiation-induction therapy is an attractive approach in leukemia treatment. It has been suggested that the accumulation of intracellular reactive oxygen species (ROS) is involved in megakaryocytic differentiation induced by phorbol 12-myristate 13-acetate (PMA) in the K562 leukemia cell line. Therefore, a ROS-inducible technique could be a powerful method of differentiation induction. Accordingly, we hypothesized that ionizing radiation contributes to the acceleration of megakaryocytic differentiation through the accumulation of intracellular ROS in leukemia cells. In the present study, ionizing radiation was shown to promote PMA-induced megakaryocytic differentiation. Cells with high CD41 expression sustained intracellular ROS levels effectively. The enhancement of differentiation by ionizing radiation was found to be regulated through the mitogen-activated protein kinase (MAPK) pathway, involving both extracellular signal-regulated protein kinase 1/2 (ERK1/2) and p38 MAPK. Ionizing radiation also controlled mRNA expression of the oxidative stress response gene heme oxygenase-1 (HO1). Consequently, we concluded that intracellular ROS, increased by ionizing radiation, modulate megakaryocytic differentiation downstream of the MAPK pathway.
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影响因子：
3.1
作者：
Conde, Isabel;Pabon, Dina;Gonzalez-Manchon, Consuelo
通讯作者：
Gonzalez-Manchon, Consuelo
影响因子：
3.4
作者：
Kato, Kengo;Takahashi, Kenji;Kashiwakura, Ikuo
通讯作者：
Kashiwakura, Ikuo
影响因子：
12.4
作者：
Sardina, J. L.;Lopez-Ruano, G.;Hernandez-Hernandez, A.
通讯作者：
Hernandez-Hernandez, A.
影响因子：
11.2
作者：
Caja, Laia;Sancho, Patricia;Fabregat, Isabel
通讯作者：
Fabregat, Isabel
DOI：
10.1002/cyto.990060614
发表时间：
1985-01-01
期刊：
CYTOMETRY
影响因子：
--
作者：
COLAMONICI, OR;TREPEL, JB;NECKERS, LM
通讯作者：
NECKERS, LM