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1.
J Cell Physiol ; 235(4): 3790-3797, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31613009

RESUMO

Acute myelocytic leukemia (AML) is an aggressive malignant tumor and typically fatal without treatment. Identification and development of novel biomarkers could be beneficial for the diagnosis and prognosis of AML patients. Here, we aimed to identify the accurate DNA methylation prognostic signatures for AML patients. The DNA methylation data of AML patients and corresponding clinical information were retrieved from The Cancer Genome Atlas database. CPG sites that correlates closely with the survival of the AML patients were identified and further combined into CPG sites pairs to screen the survival-related pairs. The prognostic signatures were identified by the C-index and forward search algorithms and validated by the verification group. Finally, the functional enrichment analysis was performed on these CPG sites. As a result, a total of 498 CPG sites associated with the overall survival of AML patients was obtained. A prognostic signature composed of 10 CPG sites pairs was obtained and validated. The functional enrichment analysis showed prognostic genes were mainly enriched in tumor protein processing, cell differentiation, blood leukocyte immunity, and platelet growth factor pathways. In summary, we identified two accurate prognostic methylation signatures (NDRG2 and TLR7), which would be served as a novel therapy target for AML.

2.
Saudi J Biol Sci ; 25(2): 242-247, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29472772

RESUMO

Objective: To investigate the role of DR4 gene in the occurrence, development and prognosis of acute myeloid leukemia (AML), find a new regulatory gene of Decitabine for the treatment of AML, namely DR4 gene, and explore the molecular mechanism of AML in the treatment of AML. Methods: The methylation level and the mRNA expression level of DR4 gene promoters of bone marrow mononuclear cells in 122 patients with newly diagnosed AML and 24 patients with iron deficiency anemia (IDA) were detected using Methylation specific PCR (MS-PCR) and Q-RT-PCR, respectively, and a correlation analysis of them was conducted. The effects of Decitabine on the proliferation of K562 cells were detected using CCK-8 assay. Then, the effects of Decitabine on the methylation level and the mRNA expression level of DR4 genes of K562 cells treated with Decitabine were detected using MS-PCR and Q-RT-PCR, respectively. The effects of Decitabine on the cell cycle and apoptosis of K562 cells were detected using flow cytometry. Results: Compared with the control group, the methylation level (P = .002) of DR4 genes of bone marrow mononuclear cells in patients with newly diagnosed AML was high. The methylation level (P = .01) of DR4 genes of bone marrow mononuclear cells in patients of the positive group of enlargement of liver, spleen and lymph node was lower than that of the negative group, and the methylation level (P = .006) of DR4 genes in patients of the high risk group of clinical stage was lower than that of the low risk group, and the methylation level (P = .03) of DR4 genes in patients of the group where patients did not achieve complete remission (CR1) after a course of induction chemotherapy was lower than that of the group where patients achieved complete remission (CR1) after a course of induction chemotherapy. There was a significant negative correlation (P < .01) between the methylation level and the mRNA expression level of DR4 genes of bone marrow mononuclear cells in 122 patients with newly diagnosed AML. After the K562 cells were treated with Decitabine for 48 h, the methylation level of DR4 gene promoters gradually decreased, while the mRNA expression level of DR4 genes gradually increased, both of which showed a concentration-dependent relationship. After the K562 cells were treated with 5 µmol/L Decitabine for 48 h, the K562 cells in G0/G1 phase and G2/M phase increased significantly, and the K562 cells in S phase decreased significantly. Conclusion: DR4 gene played an important role in the occurrence and development of AML. Decitabine can effectively inhibit the proliferation of K562 cells, which probably partly because it can terminate the methylation effect of DR4 gene promoters and restore the mRNA expression of DR4 genes.

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