Novel Functions for mda-7/IL-24 and IL-24 delE5: Regulation of Differentiation of Acute Myeloid Leukemic Cells
Novel Functions for mda-7/IL-24 and IL-24 delE5: Regulation of Differentiation of Acute Myeloid Leukemic Cells
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DOI：
10.1158/1535-7163.mct-10-0863
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发表时间：
2011-01
影响因子：
5.7
通讯作者：
Bin-Xia Yang;Y. Duan;C. Dong;Fang Zhang;Wei-Feng Gao;Xue-ying Cui;Yong-min Lin;Xiao-tong Ma
中科院分区：
文献类型：
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作者：
Bin-Xia Yang;Y. Duan;C. Dong;Fang Zhang;Wei-Feng Gao;Xue-ying Cui;Yong-min Lin;Xiao-tong Ma
对白血病细胞分化相关基因的研究有助于进一步了解白血病细胞分化的机制。本研究旨在探讨白血病细胞分化过程中黑色素瘤分化相关基因7/白细胞介素24（mda-7/IL-24）的表达是否受到诱导，以及mda-7/IL-24在白血病细胞分化过程中是否发挥作用。我们发现，在12-O-十四烷酰佛波醇-13-乙酸酯（TPA）介导的单核细胞分化过程中，U937和HL 60细胞中mda-7/IL-24和IL-24 delE 5（一种mda-7/IL-24剪接变体）的表达被诱导。丝裂原活化蛋白激酶/细胞外信号调节激酶途径的激活是其诱导所必需的。mda-7/IL-24和IL-24 delE 5的敲低导致TPA诱导的单核细胞分化的显著抑制。更重要的是，mda-7/IL-24和IL-24 delE 5的异位过表达显著诱导U937细胞、HL 60细胞和来自急性髓性白血病-M5患者的母细胞分化，而正常造血祖细胞不受影响。此外，mda-7/IL-24和IL-24 delE 5诱导选择性分化的分子效应物可能是活性氧，而活性氧的产生来源是烟酰胺腺嘌呤二核苷酸磷酸氧化酶。总之，我们的结果揭示了TPA诱导单核细胞分化的机制，并首次显示了mda-7/IL-24和IL-24 delE 5对人髓性白血病细胞的特异性分化诱导作用。Mol Cancer Ther; 10（4）; 615-25.©2011 AACR。
Characterizing genes associated with leukemic cell differentiation may provide help for understanding mechanisms on the leukemia differentiation. The aim of this study is to investigate whether the expression of melanoma differentiation-associated gene-7/interleukin-24 (mda-7/IL-24) could be induced during leukemia differentiation and whether mda-7/IL-24 plays a role in leukemia differentiation. We showed that the expression of mda-7/IL-24 and IL-24 delE5, an mda-7/IL-24 splice variant, was induced in U937 and HL60 cells during 12-O-tetradecanoylphorbol-13-acetate (TPA)-mediated monocytic differentiation. Activation of the mitogen-activated protein kinase/extracellular signal-regulated kinase pathway was required for their induction. Knockdown of mda-7/IL-24 and IL-24 delE5 resulted in significant inhibition of the monocytic differentiation induced by TPA. More importantly, ectopic overexpression of mda-7/IL-24 and IL-24 delE5 significantly induced U937 cells, HL60 cells, and blast cells from patients with acute myeloid leukemia–M5 to differentiate, whereas normal hematopoietic progenitors were not affected. Furthermore, the molecular effector associated with selective differentiation induction by mda-7/IL-24 and IL-24 delE5 may be reactive oxygen species (ROS), and the source of ROS generation was nicotinamide adenine dinucleotide phosphate oxidase. Taken together, our results reveal the mechanism by which TPA induces monocytic differentiation and show for the first time the specific differentiation-inducing effects of mda-7/IL-24 and IL-24 delE5 on human myeloid leukemic cells. Mol Cancer Ther; 10(4); 615–25. ©2011 AACR.