DNA甲基化对白血病ABO基因表达的影响

OBJECTIVE: To investigate the impact of promoter CpG island methylation on ABO mRNA expression in leukemia. METHODS: 25 cases of leukemia and 20 cases of normal control were studied, and the leukemia cell lines K562、HL-60 and Jurkat were treated with different concentrations of decitabine. PCR-SSP was used to identify ABO genotype, RQ-PCR for ABO mRNA expression and bisulfite sequencing PCR for DNA methylation status. RESULTS: ①The methylation of ABO promoter in acute myeloid leukemia patients (10 cases) and acute lymphoblastic leukemia patients (10 cases) were 53.85% and 18.22% respectively, which were obviously higher than those in control (20 cases, 2.33%) and chronic myeloid leukemia patients (5 cases, 2.12%). ②ABO genotype of K562 was O(1)O(1), which has changed little before and after decitabine treatment. ABO genotype of HL-60 and Jurkat could not been identify before treatment, but showed as O(1)A(1) and A(1)O(2) after treatment. ③ABO mRNA expression of K562 was 1 275.67 ± 35.86, which was obviously higher than that in HL-60 (0.54 ± 0.07, P<0.05) and Jurkat (0.82±0.16, P<0.05). ④The methylation of ABO promoter in K562, HL-60 and Jurkat were 0, 58.14%, and 96.74%. As concentration of decitabine increased, the methylation of ABO promoter were decreased and the expressions of ABO mRNA were increased in HL-60 and Jurkat, which had significant differences compared with that before treatment (P<0.05). CONCLUSION: The methylation of ABO promoter shows a negative correlation with ABO mRNA expression. DNA methylation was an important aspect of ABO antigens decrease in acute leukemia.