Promoter of TFPI-2 is Hypermethylated in Chinese Pediatric Acute Myeloid Leukemia

Human tissue factor pathway inhibitor-2 (TFPI-2) has been implicated as a metastasis-associated gene in many types of tumors. In this study, we investigated whether TFPI-2 was inactivated epigenetically in pediatric acute myeloid leukemia (AML). Methylation status was investigated by methylation-specific polymerase chain reaction and bisulfate genomic sequencing. TFPI-2 was aberrantly methylated in 50% (3/6) of AML cell lines. Aberrant methylation of TFPI-2 promoter was detected in 71.6% (48/67) of the Chinese pediatric AML patients. TFPI-2 transcript was significantly lower in AML group compared with controls (3.44 vs. 32.8, P<0.001). Patients with methylated TFPI-2 gene had significantly lower TFPI-2 transcript than those patients without methylated TFPI-2 (P=0.04). Promoter hypermethylation of TFPI-2 is frequent and specific event in pediatric AML.