The Expression Of DLK1, HES1 Gene In MDS And NOTCH1 Passroad In The Pathogenesis Of MDS

Background and purposeMyelodysplastic synthesis (MDS) is a group of heterogeneity, cloned hematopoietic stem cell disease, its main features are more primitive cells in bone marrow with a department or of dysplastic (pathological hematopoietic) and the transformation of risk to the risk of acute leukemia.DLK1 gene was first neuroblastoma cells were found,1557kb, located in 14q32 stretches.DLK1 widely distributed in human embryonic various tissues, the differentiation of embryonic organization plays an important adjustment function, can maintain undifferentiated cell proliferation condition. As DLK1 Ohno study found in hematopoietic progenitor cell proliferation aspects is an important regulatory factors, can inhibit the proliferation of hematopoietic progenitor cells.Notch1 pathways in evolution is a highly conservative signaling pathways, Notch1 signal is regulation cell proliferation and differentiation, important factors. Five kinds of CPC found in human Notch ligands, they are Jaggedl, Jagged2, Delta likel, Delta3 and Delta4-, including ligands Delta and DLK1 has higher homology, DLK1 can competitive and combining the ligand Notch curb Notch signal.HES1 is Notchl pathways downstream target genes, when Notchl pathways activated, increased levels of HES1 gene expression; When Notch1 pathways inhibition, HES1 gene expression levels were lower.Recent DLK1 genes in display:a high expression in patients with MDS, this experiment through trend real-time quantitatie polymerase chain reaction (PCR) DLK1 compared with patients with normal and MDS HES1 mRNA expression level of the differences and explore the possible in MDS pathogenesis mechanism of action.Patients and Methods1. Research object:21 cases from 2009-2010 in our hospital inpatient and outpatient myelodysplastic syndrome (MDS) patients,13 males,8 females, mean age 38 (16-76) years, including 12 cases of RA/RAS,9 cases of RAEB/RAEBt, Normal control group is 11 normal bone marrow in patients with non- Hematologic diseases.2. Experimental method, applied RT-PCR detected 21 cases of MDS patients and 11 patients in the control group, DLK1, and HES1 mRNA expression.3. Application SPSS 17.0 statistical software for statistical analysis. Measurement data as mean±standard deviation (±S) or median (M) said that for count data with Fisher's Exact Test test; the two samples were used to compare the number of independent samples t test and correlation analysis using Spearman test. The level ofα=0.05 as a testResults1.The expression of DLK1 mRNA in MDS patients21 cases of MDS patients DLK1 mRNA positive expression rate was 90.4% (19/21), RA/RAS expression group 0.560±0.213, RAEB/RAEB-t the expression level of 0.739±0.255, DLK1 mRNA expression between the two groups There was no significant difference (P> 0.05), the control group DLK1 mRNA positive expression rate was 9.1%(1/11), the average expression level of 0.203±0.132, and DLK1 mRNA expression levels in patients with MDS compared to the differences Statistically significant (P<0.05).2. The expression of HES1 mRNA in MDS patients21 cases of MDS patients HES1 mRNA positive expression rate was 19.0%(4/ 21), RA/RAS expression group 0.217±0.122, RAEB/RAEB-t the expression level of 0.286±0.148, HES1 mRNA expression between the two groups There was no significant difference (P> 0.05), the control group HES1 mRNA positive expression rate is 90.9%(10/11), the average expression level of 0.645±0.313, and HES1 mRNA expression levels in patients with MDS compared to the differences Statistically significant (P<0.05).3. The correlation analysis about the expression of DLKl, HES1 mRNA in MDS patients21 cases of MDS patients DLK1 and HES1-positive patients in 2 cases (9.52%), double-negative patients with 0 cases (0%), DLK1+/HES1-17 cases (80.95%), DLK1-/HES1+2 cases (9.52%). Application of 2×2 contingency table together, DLK1 and HES 1 mRNA expression in MDS patients with the association analysis, we found a negative correlation between.ConclusionDLK1 in MDS patients with high expression, HES1 in MDS patients, expression levels drop, DLK1 is highly expressed by inhibiting Notchl pathway in MDS patho-genesis played an important role, while DLK1 high expression may also be in MDS pathogenesis played an important role. Inhibit the activity of DLK1 gene level is expected to prevent the occurrence of MDS.