Identification of genes underlying different methylation profiles in refractory anemia with excess blast and refractory cytopenia with multilineage dysplasia in myelodysplastic syndrome

BACKGROUND: Myelodysplastic syndrome (MDS) is a preleukemic condition that transforms into acute myeloid leukemia. However, the genetic events underlying this transformation remain poorly understood. Aberrant DNA methylation may play a causative role in the disease and its prognosis. Thus, we compared the DNA methylation profiles in refractory anemia with excess blast (RAEB) to those in refractory cytopenia with multilineage dysplasia (RCMD). METHODS: Bone marrow samples were collected from 20 patients with primary MDS (9 with RAEB and 11 with RCMD), and peripheral blood samples were collected from 4 healthy controls. These samples were assessed using a commercial whole genome-wide methylation assay. Methylation-specific polymerase chain reaction (PCR) was used to detect the methylation of candidate gene promoters in RAEB and RCMD. RESULTS: Microarray data revealed significant hypermethylation in 69 genes within RAEB but not RCMD. Candidate genes were mapped to 5 different networks, and network 1 had the highest score due to its involvement in gene expression, cancer, and cell cycle. Five genes (GSTM5, BIK, CENPH, RERG, and ANGPTL2) were associated with malignant disease progression. Among them, the methylated promoter pairs of GSTM5 (55.5% and 20%), BIK (20% and 0%), and ANGPTL2 (44.4% and 10%) were observed more frequently in RAEB. CONCLUSION: DNA methylation of GSTM5, BIK, and ANGPTL2 may induce epigenetic silencing and contribute to the increasing blasts and resulting MDS progression; however, the functions of these genes were not determined. Further study focusing on epigenetic silencing using various detection modalities is required.

Expression of ANGPTL2 in The Kidney of Diabetic Nephropathy db/db Mice / 生物化学与生物物理进展

Kidney samples were obtained from db/db mice and their db/m littermates at the age of 4, 8, 12, 16, 20 and 24 weeks. The expression of ANGPTL2 was assessed by RT-PCR and immunohistochemistry, and then correlated with biochemical and histological indices of kidney injury. No significant difference of ANGPTL2 expression was found in the kidney of db/db mice and the control db/m mice at the age of 4 weeks, a time when all biochemical and histological indices indicated that the db/db mice were in pre-diabetic condition. However, with the development of obesity, hyperglycemia and proteinuria, the expression of ANGPTL2 in the kidney of db/db mice increased, which indicated that the increased expression of ANGPTL2 associated with diabetic nephropathy. ANGPTL2 protein was found distributed mainly in the glomerulus. It is along the capillary loop, located just outside the basement membrane, and in the same location as podocytes, which suggested that podocytes are the main origin of ANGPTL2 in the kidney. Besides, increased expression of ANGPTL2 was found in older db/m mice though it has not reached to a significant level, which may suggest that ANGPTL2 might have some thing to do with the kidney injury caused by ageing.