Expression of TFPI-2 gene and its promoter methylation in acute myeloid leukemia / 中国实验血液学杂志

ABSTRACT

The aim of this study was to detect the mRNA expression of tissue factor pathway inhibitor-2 ( TFPI-2) and its methylation in bone marrow mononuclear cells from acute myeloid leukemia (AML) patients and to explore its significance in AML. Bone marrow mononuclear cells were isolated from newly diagnosed AML patients (n = 33), complete remission AML patients (n = 19), relapsed/refractory AML patients (n = 12) and iron deficiency anemia patients (control group, n = 15). Expression of TFPI-2 mRNA was detected with real-time quantitative PCR (RT-PCR) and the methylation of CpG island in its promoter was detected with methylation-specific PCR (MSP). The results showed that the expression of TFPI-2 mRNA in newly diagnosed AML, complete remission AML and relapsed/refractory AML patients was much lower than that in the controls (P < 0.05). Furthermore, its expression in relapsed/refractory AML patients was lower than that in newly diagnosed AML patients (P = 0.006). Compared with complete remission AML patients, the expression of TFPI-2 mRNA in newly diagnosed AML patients was significantly reduced (P = 0.030). The percentage of TFPI-2 promoter methylation in AML patients was 64.63% (42/64). In newly diagnosed AML group, complete remission AML group and relapsed/refractory AML group,the percentages of TFPI-2 promoter methylation were 66.67% (22/33), 52.63% (10/19) and 83.33% (10/12) (P > 0.05), respectively. The optical density ratio of TFPI-2 mRNA expression was 0.165 (0.005-2.099) in methylated AML patients, and 0.597 (0.011-2.787) in unmethylated AML patients (P < 0.05). Methylation of TFPI-2 gene promoter was not detected in control patients. After 2 courses of chemotherapy, the level of TFPI-2 mRNA was much higher in the CR group than that in the non-CR group (P < 0.05). It is concluded that the down-regulation or silence of TFPI-2 gene potentially results from its promoter methylation, and the expression level of TFPI-2 and the methylation status of its promoter may be used as indicators of risk stratification and evaluation of disease progress.