
网络出版日期: 2013-12-03
The role of c-Myb in the pathogenesis of acute promyelocytic leukemia
Online published: 2013-12-03
目的 探讨转录因子c-Myb在急性早幼粒细胞白血病(APL)发病过程中的作用。方法 通过分析患者的表达谱数据,比较在正常早幼粒细胞和APL细胞中c-Myb的表达水平;然后通过全反式维甲酸(ATRA)诱导NB4细胞分化和PR9加ZnSO4模拟APL发病,研究c-Myb是否参与APL发病过程;利用RNAi干扰c-Myb表达的技术,明确c-Myb对逆转APL的作用。结果 在APL细胞中c-Myb的表达水平高于正常早幼粒细胞;c-Myb的表达随着ATRA的诱导分化逐渐下降,在ZnSO4诱导PR9模拟APL发病的过程中逐渐上升;c-Myb的敲除可以促进NB4细胞的分化,使NB4细胞的CD11b阳性率增加约20%。结论 APL细胞中c-Myb的表达高于正常早幼粒细胞,它对APL的发病有着重要的作用,对其选择性敲除可以部分逆转APL细胞的分化阻滞。
关键词: c-Myb; 急性早幼粒细胞白血病; 白血病转化
王 果 , 邓望龙 , 张 济 . c-Myb在急性早幼粒细胞白血病发病过程中的作用[J]. 上海交通大学学报(医学版), 2013 , 33(11) : 1475 . DOI: 10.3969/j.issn.1674-8115.2013.11.010
Objective To study the role of transcription factor c-Myb in the pathogenesis of acute promyelocytic leukemia (APL). Methods Through analyzing microarray data of acute myeloid leukemia (AML) patients, we compared the levels of c-Myb expressions in APL cells and normal promyelocytic cells. Through inducing the differentiation of NB4 with ATRA and the expression of PML-RARα in PR9 cells with ZnSO4, we investigated whether c-Myb was involved in the pathogenesis of APL. Using RNAi, we researched whether knocking down c-Myb could rescue APL. Results The levels of c-Myb expression in APL cells were higher than those in normal promyelocytic cells. The expression of c-Myb gradually declined along with the differentiation of NB4, and gradually rose along with the expression of PML-RARα in PR9. The knockdown of c-Myb could rescue the blocked differentiation of NB4, which increased the positive rate of CD11b of NB4 cells to about 20%. Conclusion The level of c-Myb expression in APL is higher than that in normal promyelocytic cells, which indicates that c-Myb has an important role in the pathogenesis of APL. The knockdown of c-Myb can partly reverse APL.
Key words: c-Myb; acute promyelocytic leukemia; leukemia transformation
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