Chemotherapy-induced hypomethylation of N-myc downstream-regulated gene 4 in the bone marrow of patients with acute myeloid leukemia

Abstract

Abstract. N-myc downstream-regulated gene 4 (NDRG4) has previously been investigated as a possible tumor suppressor. Hypermethylation of tumor suppressor genes contributes to the occurrence and development of certain types of cancer, including acute myeloid leukemia (AML). The current study aimed to assess the contribution of chemotherapy-induced NDRG4 changeable methylation to the development of AML. A total of 30 patients (13 males and 17 females) were involved in the present study. The DNA methylation levels of five C-phosphate-G sites of the NDRG4 gene were measured using bisulfite pyrosequencing techniques. The results indicated significantly reduced gene-body methylation levels of NDRG4 during chemotherapy (prior to chemotherapy: 9.35±4.22%; following chemotherapy: 7.54±3.11%; P=0.030). Further analysis of AML subtypes revealed the methylation reductions were principally contributed by patients with M2 subtype AML (prior to chemotherapy: 9.91±4.76%; following chemotherapy: 5.26±1.16%; P= 0.038). A significant association was also observed between the patient age and the altered levels of NDRG4 gene-body methylation in patients with M2 subtype AML (r=0.761; P=0.047), suggesting that reductions in induced-methylation may be age-dependent in patients with M2 subtype AML during chemotherapy. Therefore, age may affect the induced methylation levels of NDRG4 gene-body in patients with AML (particularly patients with M2 subtype AML) during chemotherapy.

A male-specific association between AGTR1 hypermethylation and coronary heart disease

“…We extracted genomic DNA from peripheral blood samples as previously described [23]. The details of bisulfite conversion and qMSP procedures are available from our previous studies [24,25]. To measure the methylation of AGTR1 promoter we calculated the percentage of methylated reference (PMR) [24,25].…”

“…The details of bisulfite conversion and qMSP procedures are available from our previous studies [24,25]. To measure the methylation of AGTR1 promoter we calculated the percentage of methylated reference (PMR) [24,25]. The primer sequences used in qMSP were forward 5'-GGAGGAGGAGGGAATGTAA-3' and reverse 5'-CCTATCACTCGCTACTACCT-3'.…”