目的：通过检测急性髓系白血病（ AML）患者骨髓液单个核细胞中FANCF／BRCA1蛋白表达及基因甲基化发生率，推测其与AML发病的相关性。方法选取2006年9月—2015年6月中国医科大学附属第一医院、秦皇岛市第一医院、大庆油田总医院血液科自愿签署试验知情同意书的AML患者101例作为研究对象（ AML组），其中初发亚组65例，缓解亚组36例；以同期就诊的贫血患者20例为对照组。提取患者骨髓液中的单个核细胞，采用Western印迹法半定量分析FANCF／BRCA1蛋白表达，应用甲基化特异性PCR（ MSP）检测FANCF／BRCA1基因的甲基化发生率。结果与对照组比较，AML组FANCF／BRCA1蛋白表达减低、FANCF／BRCA1基因甲基化率高，差异均有统计学意义（ P ＜0．05， P ＜0．01）。 FANCF与BRCA1检测结果一致：蛋白的表达均与其基因甲基化状态呈负相关性（ r ＝－0．834， P ＝0．006；r ＝－0．763， P ＝0．008）。而FANCF与BRCA1两基因的蛋白表达及甲基化无相关性（r ＝－0．051， P ＝0．821；r ＝－0．155， P ＝0．490）。结论 FANCF／BRCA1蛋白在AML患者中低表达，导致 FA／BRCA1通路中断，与AML发病可能存在相关性。 FANCF／BRCA1基因存在高度甲基化，提示两者基因高甲基化可能导致编码蛋白表达缺失，在AML的发病及进展中起到一定的作用。%Objective To detect the expression of FANCF/BRCA1 protein in bone marrow mononuclear cells of pa-tients with acute myelogenous leukemia ( AML) and the methylation incidence rate of these genes, and speculate the AML pathogenesis correlation with it.Methods From September 2006 to June 2015,101 patients diagnosed with AML in three hospital,who voluntarily signed the informed consent of the trial ,were enrolled as AML group,in which initial issuance sub-group with 65 cases and catabatic subgroup with 36 cases;in the same period,20 patients with anemia were selected as control group.The mononuclear cells were extracted from the bone marrow of negative group and AML group.Semi-quantitative West-ern blot analysis was used to detect the expression of FANCF/BRCA1 proteins and the methylation incidence of FANCF/BRCA1 gene was detected by methylation-specific PCR ( MSP) .Results Compared with the control group, the expression of FANCF/BRCA1 protein in AML group was lower , but the methylation rate of the FANCF/BRCA1 gene was higher,the signif-icance were statistical (P <0.05, P <0.01).The test results of FANCF were consistent with those of the BRCA1:the ex-pression of protein was negatively correlated with the methylation status of the gene( r =-0.834, P =0.006;r =-0.763, P =0.008).There was no correlation between methylation and protein expression of FANCF and BRCA1 two genes ( r =-0.051, P =0.821;r =-0.155, P =0.490).Conclusion The expression of FANCF/BRCA1 protein was lower in AML, which leads to disruption of the FA/BRCA1 pathway.This modification may be concerned with pathogenesis of AML.FANCF/BRCA1 gene of patients with AML shows high incidence rate of methylation,suggesting high methylation status of FANCF/BRCA1 gene may lead to an encoded protein expression deletion and play a important role in the pathogenesis and progression of AML.
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