中文摘要：

目的：探讨叉头框蛋白M1（Fox M1）及其调控的原癌基因B细胞白血病/淋巴瘤-2（bcl-2）在急性髓系白血病（AML）发生中的作用。方法：RT-q PCR和免疫荧光方法检测17例AML初诊患者、17例治疗后达完全缓解（CR）患者、17例难治复发（RR）患者和15例正常骨髓标本中Fox M1的m RNA和蛋白表达;转染Fox M1 si RNA和对照si RNA至白血病HL60细胞和K562细胞,观察Fox M1对细胞生长和克隆形成的影响,流式细胞术检测Fox M1对凋亡的影响,RT-q PCR和Western blot法检测Fox M1对Bcl-2表达的影响,双萤光素酶活性实验检测Fox M1是否可以靶向作用于bcl-2启动子区域进而影响Bcl-2的表达。结果：AML初诊患者骨髓标本的Fox M1表达较正常对照显著升高,CR患者的Fox M1表达较初诊组降低,RR组的Fox M1表达较初诊组进一步升高。转染Fox M1 si RNA沉默HL60细胞和K562细胞的Fox M1表达后,细胞生长速率显著下降,细胞克隆形成能力显著降低,细胞凋亡率显著升高,bcl-2表达降低,Fox M1可靶向调控bcl-2。结论：初步证实Fox M1可通过靶向调控bcl-2促进AML发生发展,干扰Fox M1表达可抑制细胞增殖并促进细胞凋亡,提示Fox M1是治疗AML的潜在靶标。

英文摘要：

AIM： To investigate the role of Forkhead box M1（ Fox M1） and B-cell leukemia/lymphoma-2（Bcl-2） in the pathogenesis of acute myeloid leukemia（AML）. METHODS： RT-q PCR and immunofluorescence analysis were used to determine the expression of Fox M1 at m RNA and protein levels in AML-de novo patients,AML-complete remission（ CR） patients,AML-refractoriness and relapse（ RR） patients and healthy controls. HL60 cells and K562 cells were transfected with Fox M1 si RNA. The cell proliferation was detected by cell proliferation assay and colony formation assay on soft agar,and the cell apoptosis was determined by flow cytometry. The expression of Fox M1 and Bcl-2 at m RNA and protein levels was detected by RT-q PCR and Western blotting. The activity of bcl-2 promoter was examined by luciferase reporter assay with Fox M1 targetting. RESULTS： Fox M1 expression level in the AML-de novo patients was significantly higher than that in the healthy controls. As compared with the AML-de novo patients,Fox M1 expression in the AML-CR patients was reduced,and the Fox M1 expression level was the highest in the AML-RR patients. Fox M1 expression was inhibited in the HL60 cells and K562 cells transfected with Fox M1 si RNA. Transfection with Fox M1 si RNA in the HL60 cells and K562 cells inhibited the proliferation as compared with NC si RNA transfection,and impaired the colony formation ability. On the contrary,transfection with Fox M1 si RNA promoted the cell apoptosis. Fox M1 regulated bcl-2 expression positively. CONCLUSION： Fox M1 promotes the development of AML by regulating bcl-2 expression. Silencing of Fox M1 expression suppresses cell proliferation and promotes cell apoptosis. Fox M1 is a potential target for AML treatment.